15-33473446-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001036.6(RYR3):c.79G>A(p.Ala27Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249232Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135212
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461598Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727092
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74432
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1052415). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. This variant is present in population databases (rs201612485, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 27 of the RYR3 protein (p.Ala27Thr). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at