rs786204100
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_016599.5(MYOZ2):c.773T>A(p.Val258Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,460,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V258L) has been classified as Uncertain significance.
Frequency
Consequence
NM_016599.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOZ2 | NM_016599.5 | c.773T>A | p.Val258Glu | missense_variant | 6/6 | ENST00000307128.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOZ2 | ENST00000307128.6 | c.773T>A | p.Val258Glu | missense_variant | 6/6 | 1 | NM_016599.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251010Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135682
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460420Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726632
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYOZ2-related conditions. This variant is present in population databases (rs760620614, ExAC 0.002%). This sequence change replaces valine with glutamic acid at codon 258 of the MYOZ2 protein (p.Val258Glu). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at