rs1060502965
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003673.4(TCAP):c.343G>A(p.Glu115Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,700 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E115V) has been classified as Uncertain significance.
Frequency
Consequence
NM_003673.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCAP | NM_003673.4 | c.343G>A | p.Glu115Lys | missense_variant | 2/2 | ENST00000309889.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCAP | ENST00000309889.3 | c.343G>A | p.Glu115Lys | missense_variant | 2/2 | 1 | NM_003673.4 | P1 | |
TCAP | ENST00000578283.1 | c.271G>A | p.Glu91Lys | missense_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249684Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135446
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460700Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726700
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 | Invitae | May 01, 2018 | This sequence change replaces glutamic acid with lysine at codon 115 of the TCAP protein (p.Glu115Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TCAP-related disease. ClinVar contains an entry for this variant (Variation ID: 410571). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. ClinVar contains an entry for this variant (Variation ID: 410571). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at