rs766972653
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003803.4(MYOM1):c.184C>T(p.Arg62Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000608 in 1,612,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R62H) has been classified as Uncertain significance.
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.184C>T | p.Arg62Cys | missense_variant | 2/38 | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.184C>T | p.Arg62Cys | missense_variant | 2/38 | 1 | NM_003803.4 | P2 | |
MYOM1 | ENST00000261606.11 | c.184C>T | p.Arg62Cys | missense_variant | 2/37 | 1 | A2 | ||
ENST00000580139.1 | n.198-1952G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000203 AC: 5AN: 245900Hom.: 0 AF XY: 0.0000374 AC XY: 5AN XY: 133800
GnomAD4 exome AF: 0.0000657 AC: 96AN: 1460586Hom.: 1 Cov.: 32 AF XY: 0.0000647 AC XY: 47AN XY: 726540
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.184C>T (p.R62C) alteration is located in exon 2 (coding exon 1) of the MYOM1 gene. This alteration results from a C to T substitution at nucleotide position 184, causing the arginine (R) at amino acid position 62 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 62 of the MYOM1 protein (p.Arg62Cys). This variant is present in population databases (rs766972653, gnomAD 0.004%). 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: 410261). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at