rs542350927
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4_StrongBP6
The NM_000256.3(MYBPC3):c.3472G>A(p.Val1158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,607,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000256.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.3472G>A | p.Val1158Ile | missense_variant | 31/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3472G>A | p.Val1158Ile | missense_variant | 31/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.3472G>A | p.Val1158Ile | missense_variant | 30/34 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000131 AC: 31AN: 236522Hom.: 0 AF XY: 0.000109 AC XY: 14AN XY: 128230
GnomAD4 exome AF: 0.0000296 AC: 43AN: 1454760Hom.: 0 Cov.: 35 AF XY: 0.0000263 AC XY: 19AN XY: 722926
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74472
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 24, 2013 | Val1158Ile in exon 31 of MYBPC3: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 3 mammals (orangutan, rat, and guinea pig) have an isoleucine (Ile) at thi s position despite high nearby amino acid conservation. In addition, computation al analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likelihood of imp act to the protein. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2021 | The p.V1158I variant (also known as c.3472G>A), located in coding exon 31 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 3472. The valine at codon 1158 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 03, 2021 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at