rs200713257
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_000256.3(MYBPC3):c.909C>T(p.Asp303=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,595,178 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00021 ( 5 hom. )
Consequence
MYBPC3
NM_000256.3 splice_region, synonymous
NM_000256.3 splice_region, synonymous
Scores
2
Splicing: ADA: 0.06407
1
Clinical Significance
Conservation
PhyloP100: 2.12
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.
BP6
?
Variant 11-47346644-G-A is Benign according to our data. Variant chr11-47346644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 188538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47346644-G-A is described in Lovd as [Likely_benign].
BS2
?
High Homozygotes in GnomAdExome4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.909C>T | p.Asp303= | splice_region_variant, synonymous_variant | 11/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.909C>T | p.Asp303= | splice_region_variant, synonymous_variant | 11/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.909C>T | p.Ser303= | synonymous_variant | 10/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.909C>T | p.Asp303= | splice_region_variant, synonymous_variant, NMD_transcript_variant | 11/27 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 151526Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000391 AC: 91AN: 232866Hom.: 1 AF XY: 0.000505 AC XY: 64AN XY: 126620
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GnomAD4 exome AF: 0.000208 AC: 300AN: 1443532Hom.: 5 Cov.: 45 AF XY: 0.000307 AC XY: 220AN XY: 716988
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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
Cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 04, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 18, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2016 | 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. - |
MYBPC3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 23, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at