NM_000441.2(SLC26A4):c.1061T>C (p.Phe354Ser) AND Nonsyndromic genetic hearing loss

Germline classification:: Likely benign (1 submission)
Last evaluated:: Nov 28, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003990962.1

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1061T>C (p.Phe354Ser)]

NM_000441.2(SLC26A4):c.1061T>C (p.Phe354Ser)

Gene:

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.1061T>C (p.Phe354Ser)

Other names:

NM_000441.2(SLC26A4):c.1061T>C

HGVS:

NC_000007.14:g.107689112T>C
NG_008489.1:g.33478T>C
NM_000441.2:c.1061T>CMANE SELECT
NP_000432.1:p.Phe354Ser
NC_000007.13:g.107329557T>C
NM_000441.1:c.1061T>C
c.1061T>C

Protein change:

F354S

Links:

dbSNP: rs111033243

NCBI 1000 Genomes Browser:

rs111033243

Molecular consequence:

NM_000441.2:c.1061T>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functionally_normal [Sequence Ontology: SO:0002219]

Condition(s)

Name:: Nonsyndromic genetic hearing loss
Synonyms:: Nonsyndromic hearing loss and deafness; Non-syndromic genetic deafness; Nonsyndromic genetic deafness
Identifiers:: MONDO: MONDO:0019497; MedGen: C5680182; Orphanet: 87884

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004808383	ClinGen Hearing Loss Variant Curation Expert Panel	reviewed by expert panel (Clingen Hl Acmg Specifications Cdh23 Coch Gjb2 Kcnq4 Myo6 Myo7a Slc26a4 Tecta Ush2a V2)	Likely Benign (Nov 28, 2023)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 22116359, 31599023 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004808383

ClinGen Hearing Loss Variant Curation Expert Panel

reviewed by expert panel

(Clingen Hl Acmg Specifications Cdh23 Coch Gjb2 Kcnq4 Myo6 Myo7a Slc26a4 Tecta Ush2a V2)

Likely Benign
(Nov 28, 2023)

germline

curation

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Identification of allelic variants of pendrin (SLC26A4) with loss and gain of function.

Dossena S, Bizhanova A, Nofziger C, Bernardinelli E, Ramsauer J, Kopp P, Paulmichl M.

Cell Physiol Biochem. 2011;28(3):467-76. doi: 10.1159/000335108. Epub 2011 Nov 18.

PubMed [citation]

PMID:: 22116359
PMCID:: PMC3709191

Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants.

Wasano K, Takahashi S, Rosenberg SK, Kojima T, Mutai H, Matsunaga T, Ogawa K, Homma K.

Hum Mutat. 2020 Jan;41(1):316-331. doi: 10.1002/humu.23930. Epub 2019 Oct 26.

PubMed [citation]

PMID:: 31599023
PMCID:: PMC6930342

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV004808383.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

The c.1061T>C variant in SLC26A4 is a missense variant predicted to cause substitution of phenylalanine by serine at amino acid 354 (p.Phe354Ser). The filtering allele frequency (95% CI) in gnomAD v.2.1.1 was 0.1102% (153/251206 alleles, 6 homozygotes) in Latino/Admixed American population which meets the AR threshold (>=0.07%) for BS1_P. Although the REVEL computational prediction analysis tool produced a score of 0.955, PP3 was not applied. It was observed in 3 probands with sensorineural hearing loss, however they were not scored due to the high FAF in gnomAD (PMID: 26226137, 32747562, 27861301). Functional studies have shown that this variant does not affect the ability of the protein to mediate iodide and chloride transport (PMID:22116359, 31599023) meeting BS3. In summary, this variant is likely benign for autosomal recessive nonsyndromic hearing loss based on the ACMG/AMP criteria applied as specified by the ClinGen Hearing Loss Expert Panel: BS3, BS1_P (ClinGen Hearing Loss VCEP specifications version 2; 11/28/2023)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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