rs786204329
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000256.3(MYBPC3):c.676_701dupATCACCGATGCCCAGCCTGCCTTCAC(p.Gly235SerfsTer74) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000256.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.676_701dupATCACCGATGCCCAGCCTGCCTTCAC | p.Gly235SerfsTer74 | frameshift_variant | Exon 6 of 35 | 5 | NM_000256.3 | ENSP00000442795.1 | ||
MYBPC3 | ENST00000399249.6 | c.676_701dupATCACCGATGCCCAGCCTGCCTTCAC | p.Gly235SerfsTer74 | frameshift_variant | Exon 6 of 34 | 5 | ENSP00000382193.2 | |||
MYBPC3 | ENST00000544791.1 | n.676_701dupATCACCGATGCCCAGCCTGCCTTCAC | non_coding_transcript_exon_variant | Exon 6 of 27 | 5 | ENSP00000444259.1 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461294Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726908
GnomAD4 genome Cov.: 29
ClinVar
Submissions by phenotype
not provided Pathogenic:3
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Hypertrophic cardiomyopathy Pathogenic:2
This sequence change creates a premature translational stop signal (p.Gly235Serfs*74) 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 variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 188532). For these reasons, this variant has been classified as Pathogenic. -
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Hypertrophic cardiomyopathy 4 Pathogenic:1
This variant has not been identified in large population databases (Gnomad, 1000 Genomes, Go NL, Exome Variant Server) and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at