rs377520770
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.450C>T(p.Pro150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000858 in 1,561,618 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P150P) has been classified as Likely benign.
Frequency
Consequence
NM_000256.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.450C>T | p.Pro150= | synonymous_variant | 4/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.450C>T | p.Pro150= | synonymous_variant | 4/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.450C>T | p.Pro150= | synonymous_variant | 4/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.450C>T | p.Pro150= | synonymous_variant, NMD_transcript_variant | 4/27 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000141 AC: 24AN: 170106Hom.: 0 AF XY: 0.000110 AC XY: 10AN XY: 90616
GnomAD4 exome AF: 0.0000851 AC: 120AN: 1409354Hom.: 0 Cov.: 35 AF XY: 0.0000776 AC XY: 54AN XY: 696262
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74456
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Feb 13, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2012 | Pro150Pro in exon 4 of MYBPC3: This variant is not expected to have clinical sig nificance because it does not alter an amino acid and is not located in the spli ce consensus sequence. This variant has been identified in 1/6698 European Ameri can chromosomes and 1/3314 African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Pro1 50Pro in exon 4 of MYBPC3 (allele frequency = 1/6698) ** - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 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. - |
Hypertrophic cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 22, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2015 | 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