rs778263709
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001256317.3(TMPRSS3):c.763G>T(p.Ala255Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,020 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A255V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001256317.3 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 |
---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.763G>T | p.Ala255Ser | missense_variant | 8/13 | ENST00000644384.2 | |
TMPRSS3 | NM_024022.4 | c.763G>T | p.Ala255Ser | missense_variant | 8/13 | ||
TMPRSS3 | NM_032405.2 | c.763G>T | p.Ala255Ser | missense_variant | 8/9 | ||
TMPRSS3 | NM_032404.3 | c.382G>T | p.Ala128Ser | missense_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.763G>T | p.Ala255Ser | missense_variant | 8/13 | NM_001256317.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251194Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135796
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461784Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727188
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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 | Mar 16, 2017 | The p.Ala255Ser variant in TMPRSS3 has been previously reported by our laborator y in one individual with hearing loss but without a second variant in the gene. It has been identified in 4/8642 East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs778263709). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Additional computational prediction tools and conservation analysis suggest that this variant may impact the protein, thou gh this information is not predictive enough to determine pathogenicity. In summ ary, the clinical significance of the p.Ala255Ser variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at