ClinVar Genomic variation as it relates to human health
NM_153816.6(SNX14):c.2670del (p.Lys889_Cys890insTer)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_153816.6(SNX14):c.2670del (p.Lys889_Cys890insTer)
Variation ID: 190320 Accession: VCV000190320.27
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 6q14.3 6: 85508043 (GRCh38) [ NCBI UCSC ] 6: 86217761 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 11, 2015 May 12, 2024 May 2, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_153816.6:c.2670del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_722523.1:p.Lys889_Cys890insTer nonsense NM_001297614.3:c.2643del NP_001284543.1:p.Lys880_Cys881insTer nonsense NM_001304479.2:c.2514del NP_001291408.1:p.Lys837_Cys838insTer nonsense NM_001350532.2:c.2733del NP_001337461.1:p.Lys910_Cys911insTer nonsense NM_001350533.2:c.2667del NP_001337462.1:p.Lys888_Cys889insTer nonsense NM_001350534.2:c.2640del NP_001337463.1:p.Lys879_Cys880insTer nonsense NM_001350535.2:c.2667del NP_001337464.1:p.Lys888_Cys889insTer nonsense NM_001350536.2:c.2538del NP_001337465.1:p.Lys845_Cys846insTer nonsense NM_001350537.2:c.2535del NP_001337466.1:p.Lys844_Cys845insTer nonsense NM_001350538.2:c.2526del NP_001337467.1:p.Lys841_Cys842insTer nonsense NM_001350539.2:c.2511del NP_001337468.1:p.Lys836_Cys837insTer nonsense NM_001350540.2:c.2505del NP_001337469.1:p.Lys834_Cys835insTer nonsense NM_001350541.2:c.2478del NP_001337470.1:p.Lys825_Cys826insTer nonsense NM_001350542.2:c.2382del NP_001337471.1:p.Lys793_Cys794insTer nonsense NM_001350543.2:c.2379del NP_001337472.1:p.Lys792_Cys793insTer nonsense NM_001350544.2:c.2370del NP_001337473.1:p.Lys789_Cys790insTer nonsense NM_001350545.2:c.2226del NP_001337474.1:p.Lys741_Cys742insTer nonsense NM_001350546.2:c.2226del NP_001337475.1:p.Lys741_Cys742insTer nonsense NM_001350547.2:c.1620del NP_001337476.1:p.Lys539_Cys540insTer nonsense NM_001350548.2:c.1515del NP_001337477.1:p.Lys504_Cys505insTer nonsense NM_001350549.2:c.1515del NP_001337478.1:p.Lys504_Cys505insTer nonsense NM_001350550.2:c.1515del NP_001337479.1:p.Lys504_Cys505insTer nonsense NM_001350551.2:c.1515del NP_001337480.1:p.Lys504_Cys505insTer nonsense NM_001350552.2:c.1515del NP_001337481.1:p.Lys504_Cys505insTer nonsense NM_001350553.2:c.1488del NP_001337482.1:p.Lys495_Cys496insTer nonsense NM_020468.6:c.2511del NP_065201.1:p.Lys836_Cys837insTer nonsense NR_146774.2:n.2806del non-coding transcript variant NR_146775.2:n.2809del non-coding transcript variant NR_146776.2:n.2932del non-coding transcript variant NR_146777.2:n.3060del non-coding transcript variant NR_146778.2:n.3064del non-coding transcript variant NR_146779.2:n.3061del non-coding transcript variant NC_000006.12:g.85508043del NC_000006.11:g.86217761del NG_047171.1:g.91114del - Protein change
- Other names
- NM_153816.6(SNX14):c.2670del
- p.Lys889_Cys890insTer
- Canonical SPDI
- NC_000006.12:85508042:A:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00006
Exome Aggregation Consortium (ExAC) 0.00008
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SNX14 | - | - |
GRCh38 GRCh37 |
273 | 295 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 2, 2023 | RCV000170508.7 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 27, 2023 | RCV001093187.21 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 12, 2017)
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criteria provided, single submitter
Method: research
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Autosomal recessive spinocerebellar ataxia 20
Affected status: yes
Allele origin:
paternal
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-HudsonAlpha
Accession: SCV000494577.3 First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
Number of individuals with the variant: 1
Clinical Features:
Intellectual disability, moderate (present) , Exotropia (present) , Dysmetria (present)
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Pathogenic
(Mar 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002513101.3
First in ClinVar: May 21, 2022 Last updated: Apr 09, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene … (more)
Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25848753, 34426522) (less)
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Pathogenic
(May 02, 2023)
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criteria provided, single submitter
Method: curation
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Autosomal recessive spinocerebellar ataxia 20
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003922241.1
First in ClinVar: May 06, 2023 Last updated: May 06, 2023 |
Comment:
The homozygous p.Lys889_Cys890insTer variant in SNX14 was identified by our study in one individual with spinocerebellar ataxia. The p.Lys889_Cys890insTer variant in SNX14 has been previously … (more)
The homozygous p.Lys889_Cys890insTer variant in SNX14 was identified by our study in one individual with spinocerebellar ataxia. The p.Lys889_Cys890insTer variant in SNX14 has been previously reported in 4 affected relatives from one family with autosomal recessive spinocerebellar ataxia 20 (PMID: 25848753) but has been identified in 0.01% (17/128632) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs774694340). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. These 4 affected individuals were homozygotes (PMID: 25848753), and the individual identified by our study was also a homozygote, which increases the likelihood that the p.Lys889_Cys890insTer variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 190320) and has been interpreted as pathogenic by OMIM, GeneDx, HudsonAlpha Institute for Biotechnology, and CeGaT Center for Human Genetics Tuebingen. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 889 and leads to a premature termination codon 1 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the SNX14 gene is an established disease mechanism in autosomal recessive spinocerebellar ataxia 20. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive spinocerebellar ataxia 20. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3, PP1_Moderate (Richards 2015). (less)
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Pathogenic
(Jul 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001250045.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(May 01, 2015)
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no assertion criteria provided
Method: literature only
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SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 20
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000222940.2
First in ClinVar: May 19, 2015 Last updated: Jul 09, 2018 |
Comment on evidence:
In 3 affected members of a highly consanguineous Turkish Arab family (family HMF) with autosomal recessive spinocerebellar ataxia-20 (SCAR20; 616354), Akizu et al. (2015) identified … (more)
In 3 affected members of a highly consanguineous Turkish Arab family (family HMF) with autosomal recessive spinocerebellar ataxia-20 (SCAR20; 616354), Akizu et al. (2015) identified a homozygous 1-bp deletion (c.2670delT, NM_153816.3) in the SNX14 gene, resulting in a frameshift and premature termination (Cys890Ter) in the PXC domain. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. | Akizu N | Nature genetics | 2015 | PMID: 25848753 |
Text-mined citations for rs774694340 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.