rs727503429
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000441.2(SLC26A4):āc.2063T>Cā(p.Val688Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,252,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. V688V) has been classified as Likely benign.
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.2063T>C | p.Val688Ala | missense_variant | 18/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.2063T>C | p.Val688Ala | missense_variant | 18/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000492030.2 | n.350T>C | non_coding_transcript_exon_variant | 3/6 | 5 | ||||
SLC26A4 | ENST00000644846.1 | c.745+2302T>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000439 AC: 1AN: 227720Hom.: 0 AF XY: 0.00000817 AC XY: 1AN XY: 122474
GnomAD4 exome AF: 0.00000559 AC: 7AN: 1252268Hom.: 0 Cov.: 19 AF XY: 0.00000792 AC XY: 5AN XY: 631352
GnomAD4 genome Cov.: 32
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 | Nov 19, 2013 | Variant classified as Uncertain Significance - Favor Pathogenic. The Val688Ala v ariant in SLC26A4 has not been previously reported in individuals with hearing l oss or in large population studies. Computational analyses (conservation, AlignG VGD, PolyPhen2, and SIFT) suggest that the Val688Ala variant may impact the prot ein, though this information is not predictive enough to determine pathogenicity . In summary, the clinical significance of this variant cannot be determined wi th certainty; however based upon the computational data, its absence from a larg e race matched cohort, and its presence with a likely pathogenic SLC26A4 in a he aring loss patient (this individual), we would lean towards a more likely pathog enic role. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at