chr11-47346364-C-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_000256.3(MYBPC3):āc.933G>Cā(p.Ser311=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000674 in 1,586,838 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S311S) has been classified as Likely benign.
Frequency
Consequence
NM_000256.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.933G>C | p.Ser311= | synonymous_variant | 12/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.933G>C | p.Ser311= | synonymous_variant | 12/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.933G>C | p.Ser311= | synonymous_variant | 11/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.933G>C | p.Ser311= | synonymous_variant, NMD_transcript_variant | 12/27 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 30AN: 210064Hom.: 0 AF XY: 0.000141 AC XY: 16AN XY: 113448
GnomAD4 exome AF: 0.0000683 AC: 98AN: 1434508Hom.: 0 Cov.: 32 AF XY: 0.0000760 AC XY: 54AN XY: 710640
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74480
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2014 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 18, 2013 | Ser311Ser in exon 12 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. It has been identified in 2/8430 European Am erican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washingt on.edu/EVS/). Ser311Ser in exon 12 of MYBPC3 (allele frequency = 2/8430) ** - |
Hypertrophic cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Left ventricular noncompaction 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hypertrophic cardiomyopathy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 25, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | MYBPC3: BP4, BP7 - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at