chr21-42376607-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001256317.3(TMPRSS3):c.1125C>T(p.Tyr375Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,614,020 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001256317.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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TMPRSS3 | NM_001256317.3 | c.1125C>T | p.Tyr375Tyr | synonymous_variant | Exon 11 of 13 | ENST00000644384.2 | NP_001243246.1 | |
TMPRSS3 | NM_024022.4 | c.1128C>T | p.Tyr376Tyr | synonymous_variant | Exon 11 of 13 | NP_076927.1 | ||
TMPRSS3 | NM_032404.3 | c.747C>T | p.Tyr249Tyr | synonymous_variant | Exon 8 of 10 | NP_115780.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00219 AC: 333AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00162 AC: 408AN: 251386Hom.: 0 AF XY: 0.00155 AC XY: 211AN XY: 135880
GnomAD4 exome AF: 0.00301 AC: 4403AN: 1461728Hom.: 6 Cov.: 32 AF XY: 0.00287 AC XY: 2089AN XY: 727162
GnomAD4 genome AF: 0.00220 AC: 335AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.00197 AC XY: 147AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
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TMPRSS3: BP4, BP7 -
This variant is associated with the following publications: (PMID: 11907649, 11424922) -
not specified Benign:2
Tyr376Tyr in exon 11 of TMPRSS3: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.6% (27/4427) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs111033292). -
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Autosomal recessive nonsyndromic hearing loss 8 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at