rs753671465
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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.3414C>T(p.Arg1138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,608,116 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: 0.0000062 ( 0 hom. )
Consequence
MYBPC3
NM_000256.3 synonymous
NM_000256.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0180
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=-0.43).
BP6
?
Variant 11-47332890-G-A is Benign according to our data. Variant chr11-47332890-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 188582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.018 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.3414C>T | p.Arg1138= | synonymous_variant | 31/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3414C>T | p.Arg1138= | synonymous_variant | 31/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.3414C>T | p.Arg1138= | synonymous_variant | 30/34 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000295 AC: 7AN: 237168Hom.: 0 AF XY: 0.0000388 AC XY: 5AN XY: 128738
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GnomAD4 exome AF: 0.00000618 AC: 9AN: 1455926Hom.: 0 Cov.: 35 AF XY: 0.00000691 AC XY: 5AN XY: 723606
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
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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:3
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 16, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 27, 2022 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 24, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | MYBPC3: BP4, BP7 - |
Computational scores
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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