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NM_000441.2(SLC26A4):c.1174A>T (p.Asn392Tyr)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 21, 2020
Accession:
VCV000446453.9
Variation ID:
446453
Description:
single nucleotide variant
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NM_000441.2(SLC26A4):c.1174A>T (p.Asn392Tyr)

Allele ID
439902
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q22.3
Genomic location
7: 107690148 (GRCh38) GRCh38 UCSC
7: 107330593 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.107330593A>T
NC_000007.14:g.107690148A>T
NG_008489.1:g.34514A>T
NM_000441.2:c.1174A>T MANE Select NP_000432.1:p.Asn392Tyr missense
Protein change
N392Y
Other names
-
Canonical SPDI
NC_000007.14:107690147:A:T
Functional consequence
loss_of_function_variant [Sequence Ontology SO:0002054]
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
ClinGen: CA4432714
dbSNP: rs201562855
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Aug 21, 2020 RCV000657916.3
Pathogenic 3 criteria provided, single submitter Jul 1, 2017 RCV000515717.4

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SLC26A4 - - GRCh38
GRCh37
749 825

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 01, 2017)
criteria provided, single submitter
Method: clinical testing
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
Allele origin: germline
Division of Hearing and Balance Research,National Hospital Organization Tokyo Medical Center
Accession: SCV000611812.1
Submitted: (Jul 26, 2017)
Evidence details
Pathogenic
(May 10, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000779683.1
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The N392Y missense variant has been previously reported in both the homozygous and compound heterozygous state in association with SLC26A4-related disorders (Huang et al., 2011; … (more)
Pathogenic
(Aug 21, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001224335.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces asparagine with tyrosine at codon 392 of the SLC26A4 protein (p.Asn392Tyr). The asparagine residue is highly conserved and there is a … (more)
Likely pathogenic
(Feb 26, 2019)
no assertion criteria provided
Method: case-control
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
Allele origin: inherited
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital
Accession: SCV000902368.1
Submitted: (Apr 29, 2019)
Evidence details
Affects
(Aug 20, 2019)
no assertion criteria provided
Method: clinical testing, in vitro
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct
(Autosomal recessive inheritance)
Allele origin: inherited, germline
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center
Additional submitter:
The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders,Northwestern University
Accession: SCV000994882.2
Submitted: (Oct 30, 2019)
Evidence details
Publications
PubMed (9)
Comment:
in vitro experiment

Functional evidence

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Functional consequence Method Result Submitter Supporting information
loss_of_function_variant
  1. Method not provided
  1. HCO3-/Cl- exchange_impaired; I-/Cl- exchange_normal; signal at cell membrane_negative; intracellular puncta_negative
National Institute of Sensory Organs,National Hospital Organization Tokyo Medical Center
Additional submitter:
The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders,Northwestern University
Accession: SCV000994882.2
Submitted: (Oct 30, 2019)
Evidence details
Publications
PubMed (9)

Citations for this variant

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Title Author Journal Year Link
Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants. Wasano K Human mutation 2020 PMID: 31599023
Two Compound Heterozygous Were Identified in SLC26A4 Gene in Two Chinese Families With Enlarged Vestibular Aqueduct. Yu Y Clinical and experimental otorhinolaryngology 2019 PMID: 30086623
Mapping pathogenic mutations suggests an innovative structural model for the pendrin (SLC26A4) transmembrane domain. Bassot C Biochimie 2017 PMID: 27771369
Comparative study of mutation spectrums of MT-RNR1 m.1555A>G, GJB2, and SLC26A4 between familial and sporadic patients with nonsyndromic sensorineural hearing loss in Chinese Han. Li Q Chinese medical journal 2014 PMID: 25266519
Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct. Huang S Journal of translational medicine 2011 PMID: 21961810
[An investigation of SLC26A4 gene mutation in nonsydromic hearing impairment in Hunan province of China]. Jiang L Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery 2010 PMID: 20842945
Salicylate restores transport function and anion exchanger activity of missense pendrin mutations. Ishihara K Hearing research 2010 PMID: 20826203
Mutation analysis of SLC26A4 in mainland Chinese patients with enlarged vestibular aqueduct. Reyes S Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 2009 PMID: 19786220
A distinct spectrum of SLC26A4 mutations in patients with enlarged vestibular aqueduct in China. Wang QJ Clinical genetics 2007 PMID: 17718863
Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. Park HJ Journal of medical genetics 2003 PMID: 12676893

Text-mined citations for rs201562855...

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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 Sep 29, 2021