rs201931861
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000441.2(SLC26A4):c.463A>G(p.Met155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.463A>G | p.Met155Val | missense_variant | 5/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.463A>G | p.Met155Val | missense_variant | 5/21 | NM_000441.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251478Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135920
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727244
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74424
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 21, 2016 | The p.Met155Val variant in SLC26A4 has been previously reported in at least one individual with hearing loss (Chen 2011, Haraksingh 2014); however, a variant af fecting the remaining copy of SLC26A4 was not reported. This variant was identi fied in 1/66738 European and 4/8654 East Asian chromosomes by the Exome Aggregat ion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201931861); howeve r its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p .Met155Val variant is uncertain. - |
Pendred syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2023 | Reported without a second variant in a patient with high frequency sensorineural hearing loss in published literature (Haraksingh et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21704276, 25528277) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at