rs200372325
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.3315C>T(p.Ala1105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,601,588 control chromosomes in the GnomAD database, including 1 homozygotes. 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. A1105A) 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.3315C>T | p.Ala1105= | synonymous_variant | 30/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3315C>T | p.Ala1105= | synonymous_variant | 30/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.3315C>T | p.Ala1105= | synonymous_variant | 29/34 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152118Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000443 AC: 10AN: 225832Hom.: 0 AF XY: 0.0000491 AC XY: 6AN XY: 122238
GnomAD4 exome AF: 0.0000159 AC: 23AN: 1449352Hom.: 0 Cov.: 34 AF XY: 0.0000222 AC XY: 16AN XY: 719592
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152236Hom.: 1 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74438
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 03, 2013 | Ala1105Ala in exon 30 of MYBPC3: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. The same synonymous variant resulting from a different DNA variant (3315C>A) has been identified in 2/8354 European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs200372325). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2016 | 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 | Invitae | Dec 31, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 23, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2021 | 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