17-39666078-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_003673.4(TCAP):c.473G>T(p.Arg158Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003673.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449862Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 721654
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Primary familial hypertrophic cardiomyopathy;C4225408:Hypertrophic cardiomyopathy 25 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 25, 2023 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 158 of the TCAP protein (p.Arg158Leu). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg158 amino acid residue in TCAP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26084686, 27532257; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1004753). This variant has not been reported in the literature in individuals affected with TCAP-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at