rs121909378
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM5BP4
The NM_000256.3(MYBPC3):c.3373G>T(p.Val1125Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,394 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. V1125M) has been classified as Pathogenic.
Frequency
Consequence
NM_000256.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.3373G>T | p.Val1125Leu | missense_variant | 31/35 | ENST00000545968.6 | NP_000247.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3373G>T | p.Val1125Leu | missense_variant | 31/35 | 5 | NM_000256.3 | ENSP00000442795 | P4 | |
MYBPC3 | ENST00000399249.6 | c.3373G>T | p.Val1125Leu | missense_variant | 30/34 | 5 | ENSP00000382193 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000413 AC: 1AN: 242286Hom.: 0 AF XY: 0.00000760 AC XY: 1AN XY: 131568
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1458394Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 725116
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 09, 2023 | This missense variant replaces valine with leucine at codon 1125 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has been identified in 1/242286 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 26, 2023 | This missense variant replaces valine with leucine at codon 1125 of the MYBPC3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/242286 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at