ClinVar Genomic variation as it relates to human health
NM_033409.4(SLC52A3):c.1238T>C (p.Val413Ala)
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_033409.4(SLC52A3):c.1238T>C (p.Val413Ala)
Variation ID: 144 Accession: VCV000000144.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p13 20: 761198 (GRCh38) [ NCBI UCSC ] 20: 741842 (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 1, 2015 Feb 20, 2024 May 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_033409.4:c.1238T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_212134.3:p.Val413Ala missense NM_001370085.1:c.1238T>C NP_001357014.1:p.Val413Ala missense NM_001370086.1:c.1238T>C NP_001357015.1:p.Val413Ala missense NC_000020.11:g.761198A>G NC_000020.10:g.741842A>G NG_027687.2:g.19788T>C LRG_1394:g.19788T>C LRG_1394t1:c.1238T>C LRG_1394p1:p.Val413Ala Q9NQ40:p.Val413Ala - Protein change
- V413A
- Other names
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- Canonical SPDI
- NC_000020.11:761197:A:G
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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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Exome Aggregation Consortium (ExAC) 0.00004
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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SLC52A3 | - | - |
GRCh38 GRCh37 |
437 | 501 |
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
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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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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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May 22, 2023 | RCV000000167.19 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 4, 2018 | RCV000826040.4 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
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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
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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
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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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Uncertain significance
(Apr 04, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000967531.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Val413Ala variant in SLC53A3 has been reported in the compound heterozygous state in 3 pr obands … (more)
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Val413Ala variant in SLC53A3 has been reported in the compound heterozygous state in 3 pr obands with Brown-Vialetto-Van Laere syndrome (BVVLS; Green 2010, Ciccolella 201 2, Davis 2016). It has also been identified in 3/64554 European chromosomes by t he Genome Aggregation Database (gnomAD; http://gnomad.broadinstitute.org; dbSNP rs267606687). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predi ction tools and conservation analysis suggest that the variant may not impact th e protein, though this information is not predictive enough to rule out pathogen icity. In summary, while there is some suspicion for a pathogenic role, the clin ical significance of the p.Val413Ala variant is uncertain. ACMG/AMP Criteria app lied: PM2; PM3_supporting; BP4. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Feb 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Brown-Vialetto-van Laere syndrome 1
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002579758.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PM2_SUP, PP3
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Number of individuals with the variant: 1
Sex: female
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Uncertain significance
(May 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Brown-Vialetto-van Laere syndrome 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000657509.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD … (more)
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 413 of the SLC52A3 protein (p.Val413Ala). This missense change has been observed in individuals with Brown-Vialetto-Van Laere Syndrome (BVVLS) (PMID: 20206331, 22824638, 26443808, 27777325). ClinVar contains an entry for this variant (Variation ID: 144). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC52A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Pathogenic
(Mar 17, 2015)
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no assertion criteria provided
Method: literature only
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Brown-Vialetto-Van laere syndrome
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000246226.1
First in ClinVar: Oct 01, 2015 Last updated: Oct 01, 2015 |
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Pathogenic
(Mar 12, 2010)
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no assertion criteria provided
Method: literature only
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BROWN-VIALETTO-VAN LAERE SYNDROME 1, MILD
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000020310.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2016 |
Comment on evidence:
For discussion of the val413-to-ala (V413A) mutation in the SLC52A3 gene that was found in compound heterozygous state in a patient with a mild form … (more)
For discussion of the val413-to-ala (V413A) mutation in the SLC52A3 gene that was found in compound heterozygous state in a patient with a mild form of Brown-Vialetto-Van Laere syndrome (BVVLS1; 211530) by Green et al. (2010), see 613350.0005. (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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Riboflavin Transporter Deficiency. | Adam MP | - | 2021 | PMID: 26072523 |
Remarkable motor recovery after riboflavin therapy in adult-onset Brown-Vialetto-Van Laere syndrome. | Bashford JA | Practical neurology | 2017 | PMID: 27777325 |
Brown-Vialetto-Van Laere syndrome: a 28-year follow-up. | Davis A | Journal of neurology, neurosurgery, and psychiatry | 2016 | PMID: 26443808 |
The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives. | Bosch AM | Orphanet journal of rare diseases | 2012 | PMID: 23107375 |
Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, biochemical and genetic study. | Ciccolella M | Neuromuscular disorders : NMD | 2012 | PMID: 22824638 |
Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. | Green P | American journal of human genetics | 2010 | PMID: 20206331 |
Text-mined citations for rs267606687 ...
HelpRecord last updated May 08, 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.