11-47333557-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000256.3(MYBPC3):c.3190G>A(p.Asp1064Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. 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. D1064E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000256.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.3190G>A | p.Asp1064Asn | missense_variant, splice_region_variant | 29/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3190G>A | p.Asp1064Asn | missense_variant, splice_region_variant | 29/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.3190G>A | p.Asp1064Asn | missense_variant, splice_region_variant | 28/34 | 5 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 15, 2014 | The Asp1064Asn variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction to ols and conservation analysis do not provide strong evidence for or against an i mpact the protein. However, this variant is located in the last base of the exon , which is part of the 5? splice region and computational tools predict that thi s variant may alter splicing. However, these computational tools are not predict ive enough to determine pathogenicity. Other pathogenic splice variants have bee n reported in this region (3190+1G>A, 3190+2T>G, and 3190+5G>A). In summary, the clinical significance of the Asp1064Asn variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at