rs764229797
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_016599.5(MYOZ2):āc.275T>Cā(p.Val92Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_016599.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOZ2 | NM_016599.5 | c.275T>C | p.Val92Ala | missense_variant | 4/6 | ENST00000307128.6 | |
MYOZ2 | XM_006714234.5 | c.275T>C | p.Val92Ala | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOZ2 | ENST00000307128.6 | c.275T>C | p.Val92Ala | missense_variant | 4/6 | 1 | NM_016599.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251386Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461808Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6AN XY: 727206
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 2020 | In summary, this variant has uncertain impact on MYOZ2 function. The available evidence is currently insufficient to determine its role 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a MYOZ2-related disease. This variant is present in population databases (rs764229797, ExAC 0.001%). This sequence change replaces valine with alanine at codon 92 of the MYOZ2 protein (p.Val92Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2022 | The p.V92A variant (also known as c.275T>C), located in coding exon 3 of the MYOZ2 gene, results from a T to C substitution at nucleotide position 275. The valine at codon 92 is replaced by alanine, an amino acid with 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at