19-38523059-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_000540.3(RYR1):c.10291G>C(p.Ala3431Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,984 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 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457984Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 725116
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
RYR1-related disorder 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"). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 3431 of the RYR1 protein (p.Ala3431Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at