NM_003673.4:c.16C>A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003673.4(TCAP):c.16C>A(p.Leu6Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,704 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 (★★).
Frequency
Consequence
NM_003673.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251088Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135804
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461500Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727046
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74402
ClinVar
Submissions by phenotype
not provided Uncertain:2
Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function -
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not specified Uncertain:1
The Leu6Met variant in TCAP has not been reported in the literature nor previous ly identified by our laboratory. This variant has not been identified in large a nd broad European American and African American populations by the NHLBI Exome S equencing Project (http://evs.gs.washington.edu/EVS), but was identified in 1/12 2 African American chromosomes from a broad population by the 1000 Genomes proje ct (dbSNP rs201664428). It remains possible that this variant is common in other populations. Computational analyses (biochemical amino acid properties, conserv ation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or agai nst an impact to the protein. In summary, additional information is needed to fu ll assess the clinical significance of this variant. -
Primary familial hypertrophic cardiomyopathy;C4225408:Hypertrophic cardiomyopathy 25 Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 6 of the TCAP protein (p.Leu6Met). This variant is present in population databases (rs201664428, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TCAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 44704). 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. 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