rs397515951
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.2163C>T(p.Thr721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,070 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
MYBPC3
NM_000256.3 synonymous
NM_000256.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.80
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 11-47338665-G-A is Benign according to our data. Variant chr11-47338665-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 42601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.8 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.2163C>T | p.Thr721= | synonymous_variant | 23/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.2163C>T | p.Thr721= | synonymous_variant | 23/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.2163C>T | p.Thr721= | synonymous_variant | 22/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.2163C>T | p.Thr721= | synonymous_variant, NMD_transcript_variant | 23/27 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000204 AC: 5AN: 245278Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133238
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459902Hom.: 0 Cov.: 31 AF XY: 0.00000964 AC XY: 7AN XY: 726082
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypertrophic cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 28, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 01, 2008 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 30, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at