rs200944014
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001036.6(RYR3):āc.4548C>Gā(p.Ser1516Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,591,822 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1516N) has been classified as Likely benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.4548C>G | p.Ser1516Arg | missense_variant | 34/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.4548C>G | p.Ser1516Arg | missense_variant | 34/104 | 1 | NM_001036.6 | P4 | |
RYR3 | ENST00000389232.9 | c.4548C>G | p.Ser1516Arg | missense_variant | 34/104 | 5 | A1 | ||
RYR3 | ENST00000415757.7 | c.4548C>G | p.Ser1516Arg | missense_variant | 34/103 | 2 | A2 | ||
RYR3 | ENST00000634418.1 | c.4548C>G | p.Ser1516Arg | missense_variant | 34/102 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000109 AC: 23AN: 211240Hom.: 0 AF XY: 0.000132 AC XY: 15AN XY: 113702
GnomAD4 exome AF: 0.000126 AC: 181AN: 1439646Hom.: 0 Cov.: 32 AF XY: 0.000129 AC XY: 92AN XY: 713586
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74326
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 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: 530987). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. This variant is present in population databases (rs200944014, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1516 of the RYR3 protein (p.Ser1516Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at