rs1555783458
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_000540.3(RYR1):c.7237G>A(p.Glu2413Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,670 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_000540.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.7237G>A | p.Glu2413Lys | missense_variant | Exon 45 of 106 | 5 | NM_000540.3 | ENSP00000352608.2 | ||
RYR1 | ENST00000355481.8 | c.7237G>A | p.Glu2413Lys | missense_variant | Exon 45 of 105 | 1 | ENSP00000347667.3 | |||
RYR1 | ENST00000594335.5 | n.688G>A | non_coding_transcript_exon_variant | Exon 6 of 49 | 1 | ENSP00000470927.2 | ||||
RYR1 | ENST00000599547.6 | n.7237G>A | non_coding_transcript_exon_variant | Exon 45 of 80 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151882Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461788Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0AN XY: 727196
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151882Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74178
ClinVar
Submissions by phenotype
RYR1-related disorder Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2413 of the RYR1 protein (p.Glu2413Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2420454). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RYR1 protein function. 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. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at