NM_000441.2(SLC26A4):c.416G>T (p.Gly139Val) AND Autosomal recessive nonsyndromic hearing loss 4

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 9, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002051933.2

Allele description [Variation Report for NM_000441.2(SLC26A4):c.416G>T (p.Gly139Val)]

NM_000441.2(SLC26A4):c.416G>T (p.Gly139Val)

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.416G>T (p.Gly139Val)

HGVS:

NC_000007.14:g.107674164G>T
NG_008489.1:g.18530G>T
NM_000441.2:c.416G>TMANE SELECT
NP_000432.1:p.Gly139Val
NC_000007.13:g.107314609G>T
NM_000441.1:c.416G>T

Protein change:

G139V

Links:

dbSNP: rs756272252

NCBI 1000 Genomes Browser:

rs756272252

Molecular consequence:

NM_000441.2:c.416G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 4 (DFNB4)
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 4; DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC; Nonsyndromic enlarged vestibular aqueduct (NSEVA); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010933; MedGen: C3538946; Orphanet: 90636; OMIM: 600791

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002318847	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 22, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19287372, 32447495, 23918157, 9618166, 25741868
SCV004201937	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 9, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002318847

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 22, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004201937

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 9, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

SLC26A4 mutation spectrum associated with DFNB4 deafness and Pendred's syndrome in Pakistanis.

Anwar S, Riazuddin S, Ahmed ZM, Tasneem S, Ateeq-ul-Jaleel, Khan SY, Griffith AJ, Friedman TB, Riazuddin S.

J Hum Genet. 2009 May;54(5):266-70. doi: 10.1038/jhg.2009.21. Epub 2009 Mar 13.

PubMed [citation]

PMID:: 19287372

Next-generation sequencing-based mutation analysis of genes associated with enlarged vestibular aqueduct in Chinese families.

Liu Y, Wen J, Sang S, Mei L, He C, Jiang L, Huang S, Feng Y.

Eur Arch Otorhinolaryngol. 2020 Dec;277(12):3331-3339. doi: 10.1007/s00405-020-06050-3. Epub 2020 May 23.

PubMed [citation]

PMID:: 32447495

See all PubMed Citations (5)

Details of each submission

From 3billion, SCV002318847.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SLC26A4 related disorder (ClinVar ID: VCV000996638, PMID:19287372). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 23918157). Different pathogenic/likely pathogenic amino acid change has been reported with supporting evidence at the same codon (PMID:32447495,9618166). In silico tool predictions suggest damaging effect of the variant on gene or gene product(REVEL: 0.985>=0.6, 3CNET: 0.984>=0.75). A missense variant is a common mechanism . The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000199). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Baylor Genetics, SCV004201937.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

Last Updated: Sep 29, 2024

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