chr18-3116411-C-T
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2
The NM_003803.4(MYOM1):c.3223G>A(p.Val1075Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,613,612 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
Publications
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.3223G>A | p.Val1075Met | missense_variant | Exon 21 of 38 | 1 | NM_003803.4 | ENSP00000348821.4 | ||
MYOM1 | ENST00000261606.11 | c.2935G>A | p.Val979Met | missense_variant | Exon 20 of 37 | 1 | ENSP00000261606.7 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152172Hom.: 1 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000684 AC: 17AN: 248630 AF XY: 0.0000667 show subpopulations
GnomAD4 exome AF: 0.000133 AC: 195AN: 1461440Hom.: 0 Cov.: 30 AF XY: 0.000127 AC XY: 92AN XY: 727002 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000112 AC: 17AN: 152172Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74330 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1075 of the MYOM1 protein (p.Val1075Met). This variant is present in population databases (rs371066861, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYOM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 410253). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYOM1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Cardiovascular phenotype Uncertain:1
The p.V1075M variant (also known as c.3223G>A) is located in coding exon 20 of the MYOM1 gene. This alteration results from a G to A substitution at nucleotide position 3223. The valine at codon 1075 is replaced by methionine, an amino acid with some similar properties.Based on data from the NHLBI Exome Sequencing Project (ESP), the A-allele has an overall frequency of approximately 0.02% (2/12050), having not been observed in 3794 African American alleles, and in 0.02% (2/8256) of European American alleles studied.This amino acid position is well conserved on sequence alignment.This variant is predicted to be possibly damaging by PolyPhen and deleterious by SIFT in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.V1075M remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at