rs775041835
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001036.6(RYR3):c.7462C>T(p.Arg2488Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,266 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2488L) has been classified 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.7462C>T | p.Arg2488Cys | missense_variant | 49/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.7462C>T | p.Arg2488Cys | missense_variant | 49/104 | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000684 AC: 17AN: 248580Hom.: 0 AF XY: 0.0000816 AC XY: 11AN XY: 134854
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461012Hom.: 0 Cov.: 29 AF XY: 0.0000330 AC XY: 24AN XY: 726784
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74448
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 461947). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. This variant is present in population databases (rs775041835, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2488 of the RYR3 protein (p.Arg2488Cys). - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare | Aug 03, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at