15-33473528-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001036.6(RYR3):c.161C>T(p.Ser54Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001036.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249170Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135174
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461676Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 727122
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This sequence change replaces serine with leucine at codon 54 of the RYR3 protein (p.Ser54Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs372207437, ExAC 0.002%). This variant has not been reported in the literature in individuals with RYR3-related conditions. -
Congenital myopathy 20 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at