rs3729986
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000256.3(MYBPC3):c.472G>A(p.Val158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,563,914 control chromosomes in the GnomAD database, including 6,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V158V) has been classified as Likely benign.
Frequency
Consequence
NM_000256.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 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.472G>A | p.Val158Met | missense_variant | Exon 4 of 35 | 5 | NM_000256.3 | ENSP00000442795.1 | ||
MYBPC3 | ENST00000399249.6 | c.472G>A | p.Val158Met | missense_variant | Exon 4 of 34 | 5 | ENSP00000382193.2 | |||
MYBPC3 | ENST00000544791.1 | n.472G>A | non_coding_transcript_exon_variant | Exon 4 of 27 | 5 | ENSP00000444259.1 |
Frequencies
GnomAD3 genomes AF: 0.0675 AC: 10273AN: 152132Hom.: 436 Cov.: 33
GnomAD3 exomes AF: 0.0654 AC: 11428AN: 174728Hom.: 512 AF XY: 0.0651 AC XY: 6076AN XY: 93288
GnomAD4 exome AF: 0.0895 AC: 126407AN: 1411664Hom.: 6303 Cov.: 37 AF XY: 0.0881 AC XY: 61453AN XY: 697578
GnomAD4 genome AF: 0.0675 AC: 10273AN: 152250Hom.: 436 Cov.: 33 AF XY: 0.0665 AC XY: 4951AN XY: 74458
ClinVar
Submissions by phenotype
not specified Benign:6
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Hypertrophic cardiomyopathy 4 Benign:4
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:3
This variant is associated with the following publications: (PMID: 12818575, 25342278, 14563344, 20689143) -
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Hypertrophic cardiomyopathy Benign:3
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Left ventricular noncompaction 10 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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