rs397517368
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001256317.3(TMPRSS3):c.1025G>A(p.Gly342Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,842 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 Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G342G) has been classified as Likely benign.
Frequency
Consequence
NM_001256317.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.1025G>A | p.Gly342Glu | missense_variant | 10/13 | ENST00000644384.2 | |
TMPRSS3 | NM_024022.4 | c.1025G>A | p.Gly342Glu | missense_variant | 10/13 | ||
TMPRSS3 | NM_032404.3 | c.644G>A | p.Gly215Glu | missense_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.1025G>A | p.Gly342Glu | missense_variant | 10/13 | NM_001256317.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251292Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135822
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727214
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 07, 2013 | The Gly342Glu variant in TMPRSS3 has not been identified in the general populati on but has been reported in one family with nonsyndromic hearing loss (Duman 201 1). The three affected family members tested were homozygous for this variant an d consanguinity was noted. Computational analyses (biochemical amino acid proper ties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Asp57Ala va riant may impact the protein, though this information is not predictive enough t o determine pathogenicity. In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significa nce. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at