rs376253981
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001256317.3(TMPRSS3):c.446+4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001256317.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.446+4A>T | splice_region_variant, intron_variant | ENST00000644384.2 | NP_001243246.1 | |||
TMPRSS3 | NM_024022.4 | c.446+4A>T | splice_region_variant, intron_variant | NP_076927.1 | ||||
TMPRSS3 | NM_032405.2 | c.446+4A>T | splice_region_variant, intron_variant | NP_115781.1 | ||||
TMPRSS3 | NM_032404.3 | c.65+4A>T | splice_region_variant, intron_variant | NP_115780.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.446+4A>T | splice_region_variant, intron_variant | NM_001256317.3 | ENSP00000494414.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251326Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135870
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727246
GnomAD4 genome Cov.: 33
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 | Jul 14, 2014 | The 446+4A>T variant in TMPRSS3 gene has not been previously reported in individ uals with hearing loss, but has been identified in 1/8600 European American chro mosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu; dbS NP rs376253981). This variant is located within the 5' splice consensus. Comput ational tools do not suggest an impact to splicing, though this information is n ot predictive enough to rule out pathogenicity. In summary, additional informati on is needed to fully assess the clinical significance of this variant. - |
TMPRSS3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 30, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at