rs727503201
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000256.3(MYBPC3):c.1457+6_1457+25del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MYBPC3
NM_000256.3 splice_donor_region, intron
NM_000256.3 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.20
Genes affected
MYBPC3 (HGNC:7551): (myosin binding protein C3) MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3 is expressed exclusively in heart muscle and is a key regulator of cardiac contraction. Mutations in this gene are a frequent cause of familial hypertrophic cardiomyopathy. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.1457+6_1457+25del | splice_donor_region_variant, intron_variant | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.1457+6_1457+25del | splice_donor_region_variant, intron_variant | 5 | NM_000256.3 | P4 | |||
MYBPC3 | ENST00000399249.6 | c.1457+6_1457+25del | splice_donor_region_variant, intron_variant | 5 | A2 | ||||
MYBPC3 | ENST00000544791.1 | c.1457+6_1457+25del | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 19, 2012 | Variant classified as Uncertain Significance - Favor Pathogenic. The 1457+6_1457 +25del variant in MYBPC3 has not been previously reported in the literature, but has been detected in 1 individual with HCM out of > 3300 probands (>2000 Caucas ian) tested by our laboratory and segregated with disease in four family members (including 1 obligate carrier). This variant is located in the 5' splice region and computational tools do not predict altered splicing. However, this informat ion is not predictive enough to rule out pathogenicity. While the low frequency of this variant and the segregation with disease favors a pathogenic role, we ca nnot rule out that this variant may be benign. Additional segregation studies an d functional analyses are needed to fully assess the clinical significance of th is variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at