rs397517380
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001256317.3(TMPRSS3):c.993C>T(p.Asn331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
TMPRSS3
NM_001256317.3 synonymous
NM_001256317.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.577
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 21-42380172-G-A is Benign according to our data. Variant chr21-42380172-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-42380172-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.577 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.993C>T | p.Asn331= | synonymous_variant | 10/13 | ENST00000644384.2 | |
TMPRSS3 | NM_024022.4 | c.993C>T | p.Asn331= | synonymous_variant | 10/13 | ||
TMPRSS3 | NM_032404.3 | c.612C>T | p.Asn204= | synonymous_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.993C>T | p.Asn331= | synonymous_variant | 10/13 | NM_001256317.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000143 AC: 36AN: 251370Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135860
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GnomAD4 exome AF: 0.000112 AC: 164AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 104AN XY: 727230
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 01, 2014 | Asn331Asn in exon 10 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at