rs2839501
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001256317.3(TMPRSS3):c.453G>A(p.Val151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,612,724 control chromosomes in the GnomAD database, including 121,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.48 ( 20835 hom., cov: 32)
Exomes 𝑓: 0.36 ( 100230 hom. )
Consequence
TMPRSS3
NM_001256317.3 synonymous
NM_001256317.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.09
Genes affected
TMPRSS3 (HGNC:11877): (transmembrane serine protease 3) This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a serine protease domain, a transmembrane domain, an LDL receptor-like domain, and a scavenger receptor cysteine-rich domain. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified by its association with both congenital and childhood onset autosomal recessive deafness. This gene is expressed in fetal cochlea and many other tissues, and is thought to be involved in the development and maintenance of the inner ear or the contents of the perilymph and endolymph. This gene was also identified as a tumor-associated gene that is overexpressed in ovarian tumors. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 21-42385528-C-T is Benign according to our data. Variant chr21-42385528-C-T is described in ClinVar as [Benign]. Clinvar id is 46122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-42385528-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.09 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.453G>A | p.Val151= | synonymous_variant | 6/13 | ENST00000644384.2 | |
TMPRSS3 | NM_024022.4 | c.453G>A | p.Val151= | synonymous_variant | 6/13 | ||
TMPRSS3 | NM_032405.2 | c.453G>A | p.Val151= | synonymous_variant | 6/9 | ||
TMPRSS3 | NM_032404.3 | c.72G>A | p.Val24= | synonymous_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.453G>A | p.Val151= | synonymous_variant | 6/13 | NM_001256317.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.478 AC: 72603AN: 151956Hom.: 20783 Cov.: 32
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GnomAD3 exomes AF: 0.360 AC: 90420AN: 251436Hom.: 18239 AF XY: 0.352 AC XY: 47819AN XY: 135906
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GnomAD4 exome AF: 0.362 AC: 528370AN: 1460650Hom.: 100230 Cov.: 44 AF XY: 0.359 AC XY: 260652AN XY: 726732
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GnomAD4 genome ? AF: 0.478 AC: 72716AN: 152074Hom.: 20835 Cov.: 32 AF XY: 0.469 AC XY: 34850AN XY: 74314
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
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 | - | - - |
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. - |
Autosomal recessive nonsyndromic hearing loss 8 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at