ClinVar Genomic variation as it relates to human health
NM_000441.2(SLC26A4):c.17G>T (p.Gly6Val)
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.
Uncertain significance(1); Benign(5); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000441.2(SLC26A4):c.17G>T (p.Gly6Val)
Variation ID: 43524 Accession: VCV000043524.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q22.3 7: 107661658 (GRCh38) [ NCBI UCSC ] 7: 107302103 (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 Mar 29, 2015 Feb 14, 2024 Jan 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000441.2:c.17G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000432.1:p.Gly6Val missense NR_028137.1:n.141C>A non-coding transcript variant NC_000007.14:g.107661658G>T NC_000007.13:g.107302103G>T NG_008489.1:g.6024G>T O43511:p.Gly6Val - Protein change
- G6V
- Other names
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- Canonical SPDI
- NC_000007.14:107661657:G:T
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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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0.00799 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD) 0.00010
Trans-Omics for Precision Medicine (TOPMed) 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00248
1000 Genomes Project 30x 0.00750
1000 Genomes Project 0.00799
Exome Aggregation Consortium (ExAC) 0.00981
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
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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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SLC26A4 | - | - |
GRCh38 GRCh37 |
1376 | 1574 | |
SLC26A4-AS1 | - | - | - | GRCh38 | - | 104 |
Conditions - Germline
Condition
Help
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
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. |
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Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jul 12, 2022 | RCV000036459.9 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Sep 5, 2021 | RCV000169379.10 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 27, 2024 | RCV000757777.20 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Sep 5, 2021 | RCV001164583.8 |
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
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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
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
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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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Likely benign
(Jan 23, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000886132.1
First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019 |
Comment:
The c.17G>T; p.Gly6Val variant (rs111033423, ClinVar variant ID 43524) has been reported in patients with hearing loss (Pourova 2010, Tang 2015) and congenital hypothyroidism (de … (more)
The c.17G>T; p.Gly6Val variant (rs111033423, ClinVar variant ID 43524) has been reported in patients with hearing loss (Pourova 2010, Tang 2015) and congenital hypothyroidism (de Filippis 2017); however, it was also detected at a similar frequency in a control population (Pourova 2010). This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 1.6% (identified on 398 out of 25,068 chromosomes, including 6 homozygotes). The glycine at position 6 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Gly6Val variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the p.Gly6Val variant is likely to be benign. (less)
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Benign
(Apr 25, 2017)
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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: SCV000060114.6
First in ClinVar: May 03, 2013 Last updated: May 03, 2018 |
Comment:
The p.Gly6Val variant in exon 2 of SLC26A4: This variant is not expected to have clinical significance because it has been identified in 1.6% (398/25068) … (more)
The p.Gly6Val variant in exon 2 of SLC26A4: This variant is not expected to have clinical significance because it has been identified in 1.6% (398/25068) of Sou th Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.b roadinstitute.org; dbSNP rs111033423). (less)
Number of individuals with the variant: 4
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Benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Pendred syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001326716.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001326717.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Benign
(Sep 30, 2019)
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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: SCV000731038.2
First in ClinVar: Apr 09, 2018 Last updated: Jul 24, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 28444304, 20597900, 25991456, 26188157, 20601923)
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Benign
(Jul 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002570598.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: SLC26A4 c.17G>T (p.Gly6Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Variant summary: SLC26A4 c.17G>T (p.Gly6Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0025 in 177348 control chromosomes, predominantly at a frequency of 0.016 within the South Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 5 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC26A4 causing Pendred Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Eight ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1), likely benign (n=2) and benign (n=5). Based on the evidence outlined above, the variant was classified as benign. (less)
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Likely benign
(Oct 17, 2014)
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criteria provided, single submitter
Method: literature only
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Pendred's syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220767.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Benign
(Jan 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001067872.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Likely benign
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 4
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027117.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Likely benign
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Pendred syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027228.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Benign
(Nov 11, 2019)
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no assertion criteria provided
Method: clinical testing
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Pendred syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002079957.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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DNA sequence analysis and genotype-phenotype assessment in 71 patients with syndromic hearing loss or auditory neuropathy. | Tang HY | BMJ open | 2015 | PMID: 25991456 |
Prevalence of Connexin 26 (GJB2) and Pendred (SLC26A4) mutations in a population of adult cochlear implant candidates. | Hochman JB | Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology | 2010 | PMID: 20601923 |
Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA). | Pourová R | Annals of human genetics | 2010 | PMID: 20597900 |
Text-mined citations for rs111033423 ...
HelpRecord last updated Sep 29, 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.