rs373730381
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000256.3(MYBPC3):c.787G>T(p.Gly263*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000256.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.787G>T | p.Gly263* | stop_gained | Exon 7 of 35 | 5 | NM_000256.3 | ENSP00000442795.1 | ||
MYBPC3 | ENST00000399249.6 | c.787G>T | p.Gly263* | stop_gained | Exon 7 of 34 | 5 | ENSP00000382193.2 | |||
MYBPC3 | ENST00000544791.1 | n.787G>T | non_coding_transcript_exon_variant | Exon 7 of 27 | 5 | ENSP00000444259.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1420684Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 702726
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Pathogenic:1
This sequence change creates a premature translational stop signal (p.Gly263*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 19150014, 22765922, 29631964). ClinVar contains an entry for this variant (Variation ID: 1460339). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -
Cardiovascular phenotype Pathogenic:1
The p.G263* pathogenic mutation (also known as c.787G>T), located in coding exon 7 of the MYBPC3 gene, results from a G to T substitution at nucleotide position 787. This changes the amino acid from a glycine to a stop codon within coding exon 7. This variant has been detected in probands with hypertrophic cardiomyopathy, and has been reported as a common mutation in Spain (García-Castro M et al. Rev Esp Cardiol. 2009 Jan;62:48-56; Gómez J et al. Circ Cardiovasc Genet. 2017 Apr;10(2); Lorca R et al. J Clin Med. 2020 Aug;9(8)). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.