rs377292092
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.12G>A(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,596,194 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 (★★).
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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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MYBPC3 | ENST00000545968.6 | c.12G>A | p.Pro4Pro | synonymous_variant | Exon 1 of 35 | 5 | NM_000256.3 | ENSP00000442795.1 | ||
MYBPC3 | ENST00000399249.6 | c.12G>A | p.Pro4Pro | synonymous_variant | Exon 1 of 34 | 5 | ENSP00000382193.2 | |||
MYBPC3 | ENST00000544791.1 | n.12G>A | non_coding_transcript_exon_variant | Exon 1 of 27 | 5 | ENSP00000444259.1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152028Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000949 AC: 22AN: 231718Hom.: 0 AF XY: 0.0000869 AC XY: 11AN XY: 126540
GnomAD4 exome AF: 0.000145 AC: 209AN: 1444166Hom.: 0 Cov.: 30 AF XY: 0.000152 AC XY: 109AN XY: 718312
GnomAD4 genome AF: 0.000118 AC: 18AN: 152028Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74258
ClinVar
Submissions by phenotype
not specified Benign:3
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. -
Pro4Pro in exon 1 of MYBPC3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. -
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Cardiomyopathy Benign:2
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not provided Benign:2
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Hypertrophic cardiomyopathy Benign:2
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Hypertrophic cardiomyopathy 4 Benign:1
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Cardiovascular phenotype Benign:1
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
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at