ClinVar Genomic variation as it relates to human health
NM_014297.5(ETHE1):c.6G>A (p.Ala2=)
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
-
NM_014297.5(ETHE1):c.6G>A (p.Ala2=)
Variation ID: 260385 Accession: VCV000260385.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19q13.31 19: 43527172 (GRCh38) [ NCBI UCSC ] 19: 44031324 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 3, 2016 Feb 20, 2024 May 7, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_014297.5(ETHE1):c.6G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_014297.5:c.6G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055112.2:p.Ala2= synonymous NM_001320867.2:c.6G>A NP_001307796.1:p.Ala2= synonymous NM_001320868.2:c.-215G>A 5 prime UTR NM_001320869.2:c.6G>A NP_001307798.1:p.Ala2= synonymous NC_000019.10:g.43527172C>T NC_000019.9:g.44031324C>T NG_008141.1:g.5073G>A - Protein change
- Other names
- -
- Canonical SPDI
- NC_000019.10:43527171:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.15236 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.14891
1000 Genomes Project 0.15236
The Genome Aggregation Database (gnomAD), exomes 0.15717
Trans-Omics for Precision Medicine (TOPMed) 0.16273
The Genome Aggregation Database (gnomAD) 0.17604
Exome Aggregation Consortium (ExAC) 0.19066
1000 Genomes Project 30x 0.14710
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
ETHE1 | - | - |
GRCh38 GRCh37 |
394 | 432 | |
LOC130064595 | - | - | - | GRCh38 | - | 27 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2018 | RCV000251048.6 | |
Benign (5) |
reviewed by expert panel
|
May 7, 2021 | RCV000379794.15 | |
Benign (2) |
criteria provided, single submitter
|
Mar 3, 2015 | RCV000676454.6 |
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. |
|
---|---|---|---|---|---|
Benign
(May 07, 2021)
|
reviewed by expert panel
Method: curation
|
Ethylmalonic encephalopathy
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen
Accession: SCV001736737.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Comment:
The allele frequency of the c.6G>A variant in the ETHE1 gene is reported as >16% in gnomAD, including >2,000 homozygotes, which is high enough to … (more)
The allele frequency of the c.6G>A variant in the ETHE1 gene is reported as >16% in gnomAD, including >2,000 homozygotes, which is high enough to be classified as benign based on thresholds defined by the ClinGen ETHE1 Variant Curation Expert Panel (>0.1% in gnomAD- BA1 and BS2). In silico splicing predictors (Splice AI) do not predict a deleterious effect (BP7). In summary, this variant meets criteria to be classified as benign for ETHE1-related ethylmalonic encephalopathy. ETHE1-specific ACMG/AMP criteria applied: (BA1, BS2, BP7). (less)
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000312130.1
First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016 |
|
|
Benign
(Feb 05, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917321.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: ETHE1 c.6G>A alters a non-conserved nucleotide resulting in a synonymous change. Four computational tools predict the variant has no significant impact on splicing … (more)
Variant summary: ETHE1 c.6G>A alters a non-conserved nucleotide resulting in a synonymous change. Four computational tools predict the variant has no significant impact on splicing while one predicts the variant strengthens a cryptic 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.16 in 159212 control chromosomes in the gnomAD database, including 2280 homozygotes. The observed variant frequency is approximately 122-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in ETHE1 causing Ethylmalonic Encephalopathy phenotype (0.0013), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.6G>A in individuals affected with Ethylmalonic Encephalopathy and no experimental evidence demonstrating its impact on protein function have been reported. A clinical diagnostic laboratory has a ClinVar submission after 2014 with a classification of "benign," along with another clinical diagnostic laboratory with no submission date as "benign." Based on the evidence outlined above, the variant was classified as benign. (less)
|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Ethylmalonic encephalopathy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000413496.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
Benign
(Jul 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Ethylmalonic encephalopathy
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001761404.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
Sex: mixed
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001903759.1
First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ethylmalonic encephalopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001717946.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
|
Benign
(Feb 15, 2016)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000802236.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
Benign
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Ethylmalonic encephalopathy
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001454617.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
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 |
---|---|---|---|---|
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/1931d802-2e7e-48dd-b06f-68f862cfb491 | - | - | - | - |
Text-mined citations for rs3810381 ...
HelpRecord last updated Mar 11, 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.