rs397517370
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001256317.3(TMPRSS3):c.1087T>G(p.Leu363Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
TMPRSS3
NM_001256317.3 missense
NM_001256317.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 0.658
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
In a disulfide_bond (size 69) in uniprot entity TMPS3_HUMAN there are 21 pathogenic changes around while only 2 benign (91%) in NM_001256317.3
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPRSS3 | NM_001256317.3 | c.1087T>G | p.Leu363Val | missense_variant | 11/13 | ENST00000644384.2 | |
TMPRSS3 | NM_024022.4 | c.1090T>G | p.Leu364Val | missense_variant | 11/13 | ||
TMPRSS3 | NM_032404.3 | c.709T>G | p.Leu237Val | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPRSS3 | ENST00000644384.2 | c.1087T>G | p.Leu363Val | missense_variant | 11/13 | NM_001256317.3 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
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 23, 2012 | The Leu364Val variant in TMPRSS3 has not been reported in the literature nor pre viously identified by our laboratory. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Leu364Val variant may impact the protein, though this information is not predict ive enough to determine pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;N;N;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;N;N
REVEL
Uncertain
Sift
Uncertain
.;.;D;D
Sift4G
Uncertain
.;.;D;D
Polyphen
D;D;D;D
Vest4
0.67, 0.65
MutPred
0.52
.;Gain of methylation at K368 (P = 0.0633);Gain of methylation at K368 (P = 0.0633);.;
MVP
0.71
MPC
0.53
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at