rs727503193
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.1935C>T(p.Pro645=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,362 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. P645P) 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.1935C>T | p.Pro645= | synonymous_variant | 21/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.1935C>T | p.Pro645= | synonymous_variant | 21/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.1935C>T | p.Pro645= | synonymous_variant | 20/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.1935C>T | p.Pro645= | synonymous_variant, NMD_transcript_variant | 21/27 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249024Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135106
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461164Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726772
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 07, 2014 | Pro645Pro in exon 21 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. - |
Hypertrophic cardiomyopathy 4;C3715165:Left ventricular noncompaction 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 15, 2021 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 08, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | 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. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 12, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at