VCV000043515.30 - ClinVar

NM_000441.2(SLC26A4):c.15C>A (p.Gly5=)

Germline

Classification

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.

(12)

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.

Conflicting classifications of pathogenicity
Uncertain significance(2); Benign(6); Likely benign(3)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000441.2(SLC26A4):c.15C>A (p.Gly5=)

Variation ID: 43515 Accession: VCV000043515.30

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.3 7: 107661656 (GRCh38) [ NCBI UCSC ] 7: 107302101 (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	Apr 9, 2018	Dec 22, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000441.2:c.15C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000432.1:p.Gly5=	synonymous
NR_028137.1:n.143G>T		non-coding transcript variant
NC_000007.14:g.107661656C>A
NC_000007.13:g.107302101C>A
NG_008489.1:g.6022C>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:107661655:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00599 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00145

Exome Aggregation Consortium (ExAC) 0.00350

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00468

1000 Genomes Project 30x 0.00593

1000 Genomes Project 0.00599

Trans-Omics for Precision Medicine (TOPMed) 0.00635

The Genome Aggregation Database (gnomAD) 0.00669

Links

ClinGen: CA132669 dbSNP: rs7811324 VarSome

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
Gene	OMIM	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.
SLC26A4		-	-	GRCh38 GRCh37	1396	1597
SLC26A4-AS1	-	-	-	GRCh38	-	105

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.
not specified	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 13, 2018	RCV000036450.11
Pendred syndrome	Conflicting classifications of pathogenicity (4)	criteria provided, conflicting classifications	Sep 5, 2021	RCV000674869.12
not provided	Benign (4)	criteria provided, multiple submitters, no conflicts	Aug 1, 2024	RCV000956517.16
Autosomal recessive nonsyndromic hearing loss 4	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Sep 5, 2021	RCV001164582.9

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.
Likely benign (May 29, 2018)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Pendred syndrome Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000800273.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018	Publications: PubMed (1) PubMed: 23280318
Benign (Aug 24, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060105.6 First in ClinVar: May 03, 2013 Last updated: May 03, 2018	Comment: Gly5Gly in exon 2 of SLC26A4: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, … (more) Gly5Gly in exon 2 of SLC26A4: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 1.4% (54/3922) of African American chromosomes from a broad population by the NHLBI Exome sequencing proje ct (http://evs.gs.washington.edu/EVS/). (less) Number of individuals with the variant: 7
Benign (Feb 22, 2019)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001145685.1 First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020	Publications: PubMed (3) PubMed: 23280318‚ 29739340‚ 30068397
Uncertain significance (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Pendred syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001324483.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (1) PubMed: 23280318 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)
Uncertain significance (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Autosomal recessive nonsyndromic hearing loss 4 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001326715.1 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
Benign (Dec 23, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000721595.2 First in ClinVar: Apr 09, 2018 Last updated: Sep 29, 2021	Comment: This variant is associated with the following publications: (PMID: 29739340, 23280318)
Benign (Feb 13, 2018)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000859388.1 First in ClinVar: May 03, 2018 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC26A4 http://gnomad.broadinstitute.org… http://gnomad.broadinstitute.org/region/7-107302001-107302201 Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed
Likely benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive nonsyndromic hearing loss 4 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002026697.1 First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021
Likely benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pendred syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002027006.1 First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001103283.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV005093355.4 First in ClinVar: Aug 04, 2024 Last updated: Dec 22, 2024	Comment: SLC26A4: BP4, BP7, BS1, BS2; SLC26A4-AS1: BS1, BS2 Number of individuals with the variant: 2
Benign (Oct 18, 2019)	no assertion criteria provided Method: clinical testing	Pendred syndrome Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002079956.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022
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Comment:

Gly5Gly in exon 2 of SLC26A4: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, has been identified in 1.4% (54/3922) of African American chromosomes from a broad population by the NHLBI Exome sequencing proje ct (http://evs.gs.washington.edu/EVS/).

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, 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.

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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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.

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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Contribution of SLC26A4 to the molecular diagnosis of nonsyndromic prelingual sensorineural hearing loss in a Brazilian cohort.	Carvalho SDCES	BMC research notes	2018	PMID: 30068397
Mutation analysis of SLC26A4 (Pendrin) gene in a Brazilian sample of hearing-impaired subjects.	Nonose RW	BMC medical genetics	2018	PMID: 29739340
Screening of SLC26A4 gene in autoimmune thyroid diseases.	Kallel R	International journal of immunogenetics	2013	PMID: 23280318
http://gnomad.broadinstitute.org/region/7-107302001-107302201	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC26A4	-	-	-	-

Text-mined citations for rs7811324 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 19, 2025

ClinVar Genomic variation as it relates to human health

NM_000441.2(SLC26A4):c.15C>A (p.Gly5=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs7811324 ...