rs397515932
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.1869C>T(p.Cys623=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,591,654 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 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
MYBPC3
NM_000256.3 synonymous
NM_000256.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.36
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 11-47341166-G-A is Benign according to our data. Variant chr11-47341166-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 42579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.36 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.1869C>T | p.Cys623= | synonymous_variant | 19/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.1869C>T | p.Cys623= | synonymous_variant | 19/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.1869C>T | p.Cys623= | synonymous_variant | 18/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.1869C>T | p.Cys623= | synonymous_variant, NMD_transcript_variant | 19/27 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151708Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000220 AC: 5AN: 227142Hom.: 0 AF XY: 0.0000406 AC XY: 5AN XY: 123030
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GnomAD4 exome AF: 0.0000174 AC: 25AN: 1439946Hom.: 0 Cov.: 36 AF XY: 0.0000168 AC XY: 12AN XY: 714792
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GnomAD4 genome AF: 0.0000461 AC: 7AN: 151708Hom.: 0 Cov.: 33 AF XY: 0.0000540 AC XY: 4AN XY: 74112
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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
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 24, 2012 | Cys623Cys in exon 19 of MYBPC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. Cys623Cys in exon 19 of MYBPC3 (allele freq uency = n/a) - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 08, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 03, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 20, 2017 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 10, 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at