rs373058706
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_001256317.3(TMPRSS3):c.310G>A(p.Glu104Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,852 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. E104E) has been classified as Likely benign.
Frequency
Consequence
NM_001256317.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.310G>A | p.Glu104Lys | missense_variant | 4/13 | ENST00000644384.2 | |
TMPRSS3 | NM_024022.4 | c.310G>A | p.Glu104Lys | missense_variant | 4/13 | ||
TMPRSS3 | NM_032405.2 | c.310G>A | p.Glu104Lys | missense_variant | 4/9 | ||
TMPRSS3 | NM_032404.3 | c.-72G>A | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.310G>A | p.Glu104Lys | missense_variant | 4/13 | NM_001256317.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251460Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461620Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727132
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 8 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | The Shared Resource Centre "Genome", Research Centre for Medical Genetics | Nov 10, 2022 | - - |
Rare genetic deafness Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 02, 2016 | The p.Glu104Lys variant in TMPRSS3 has been reported in the homozygous state in 1 Pakistani individual with hearing loss and segregated in 6 affected relatives whose parents were consanguineous (Lee 2012). This variant has been identified i n 2/66672 of European chromosomes by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org; dbSNP rs373058706); however, its frequency is low e nough to be consistent with a recessive carrier frequency. In summary, although additional studies are required to fully establish its clinical significance, t his variant is likely pathogenic for autosomal recessive nonsyndromic hearing lo ss. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at