chr17-39665865-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_003673.4(TCAP):βc.260G>Aβ(p.Arg87Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,610,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87W) has been classified as Likely benign.
Frequency
Consequence
NM_003673.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000412 AC: 1AN: 242504Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132386
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1458662Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 725524
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 27, 2025 | Reported in a patient with dilated cardiomyopathy (PMID: 12507422); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 15582318, 23299917, 16490376, 12507422, 36129056, 24843229, 21360311, 36935760) - |
Hypertrophic cardiomyopathy 4 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Institut fΓΌr Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen | May 01, 2016 | - - |
Hypertrophic cardiomyopathy 25 Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Dec 07, 2004 | - - |
Primary familial hypertrophic cardiomyopathy;C4225408:Hypertrophic cardiomyopathy 25 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 10, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 87 of the TCAP protein (p.Arg87Gln). This variant is present in population databases (rs121434298, gnomAD 0.0009%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 12507422). ClinVar contains an entry for this variant (Variation ID: 5527). 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. Experimental studies have shown that this missense change affects TCAP function (PMID: 15582318). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at