rs553113819
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_000540.3(RYR1):c.10291G>A(p.Ala3431Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000041 in 1,609,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A3431V) has been classified 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.10291G>A | p.Ala3431Thr | missense_variant | 68/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.10291G>A | p.Ala3431Thr | missense_variant | 68/106 | 5 | NM_000540.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000330 AC: 5AN: 151706Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000369 AC: 9AN: 243864Hom.: 0 AF XY: 0.0000378 AC XY: 5AN XY: 132334
GnomAD4 exome AF: 0.0000418 AC: 61AN: 1457984Hom.: 0 Cov.: 33 AF XY: 0.0000483 AC XY: 35AN XY: 725116
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 151824Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74188
ClinVar
Submissions by phenotype
RYR1-Related Disorders Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces alanine with threonine at codon 3431 of the RYR1 protein (p.Ala3431Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs553113819, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at