rs2839500
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_001256317.3(TMPRSS3):āc.757A>Gā(p.Ile253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,874 control chromosomes in the GnomAD database, including 16,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_001256317.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.757A>G | p.Ile253Val | missense_variant | 8/13 | ENST00000644384.2 | NP_001243246.1 | |
TMPRSS3 | NM_024022.4 | c.757A>G | p.Ile253Val | missense_variant | 8/13 | NP_076927.1 | ||
TMPRSS3 | NM_032405.2 | c.757A>G | p.Ile253Val | missense_variant | 8/9 | NP_115781.1 | ||
TMPRSS3 | NM_032404.3 | c.376A>G | p.Ile126Val | missense_variant | 5/10 | NP_115780.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.757A>G | p.Ile253Val | missense_variant | 8/13 | NM_001256317.3 | ENSP00000494414 | A1 |
Frequencies
GnomAD3 genomes AF: 0.169 AC: 25634AN: 152080Hom.: 2734 Cov.: 33
GnomAD3 exomes AF: 0.156 AC: 39280AN: 251026Hom.: 3865 AF XY: 0.158 AC XY: 21420AN XY: 135714
GnomAD4 exome AF: 0.126 AC: 184862AN: 1461674Hom.: 14078 Cov.: 32 AF XY: 0.129 AC XY: 93978AN XY: 727142
GnomAD4 genome AF: 0.169 AC: 25680AN: 152200Hom.: 2742 Cov.: 33 AF XY: 0.170 AC XY: 12627AN XY: 74422
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 16, 2007 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive nonsyndromic hearing loss 8 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at