rs11570105
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000256.3(MYBPC3):c.2603-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,476,020 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
MYBPC3
NM_000256.3 splice_polypyrimidine_tract, intron
NM_000256.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00008853
2
Clinical Significance
Conservation
PhyloP100: -0.0380
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 Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 11-47336022-G-A is Benign according to our data. Variant chr11-47336022-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.2603-11C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.2603-11C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000256.3 | P4 | |||
MYBPC3 | ENST00000399249.6 | c.2603-11C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | A2 | ||||
MYBPC3 | ENST00000544791.1 | c.*108-11C>T | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152196Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000281 AC: 4AN: 142468Hom.: 0 AF XY: 0.0000391 AC XY: 3AN XY: 76730
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GnomAD4 exome AF: 0.0000453 AC: 60AN: 1323824Hom.: 0 Cov.: 34 AF XY: 0.0000495 AC XY: 32AN XY: 646790
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152196Hom.: 0 Cov.: 30 AF XY: 0.0000538 AC XY: 4AN XY: 74352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypertrophic cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 26, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 18, 2014 | c.2603-11C>T in intron 25 of MYBPC3: This variant is not expected to have clinic al significance because a C>T change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 08, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 03, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at