NM_000441.2(SLC26A4):c.416G>T (p.Gly139Val) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Sep 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001378586.1

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

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001576188Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 20, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China.

Chai Y, Huang Z, Tao Z, Li X, Li L, Li Y, Wu H, Yang T.

Am J Med Genet A. 2013 Sep;161A(9):2226-33. doi: 10.1002/ajmg.a.36068. Epub 2013 Aug 5.

PubMed [citation]
PMID:
23918157
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001576188.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces glycine with valine at codon 139 of the SLC26A4 protein (p.Gly139Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs756272252, ExAC 0.03%). This variant has been observed in individual(s) with clinical features of Pendred syndrome (PMID: 19287372, 23918157, 25317404). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Gly139 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC26A4-related conditions (PMID: 9618166), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 6, 2021

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