rs771903948
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001036.6(RYR3):c.160T>G(p.Ser54Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,888 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. S54L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.160T>G | p.Ser54Ala | missense_variant | 2/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.160T>G | p.Ser54Ala | missense_variant | 2/104 | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461678Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727124
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2020 | 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 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 with RYR3-related disease. This variant is present in population databases (rs771903948, ExAC 0.002%). This sequence change replaces serine with alanine at codon 54 of the RYR3 protein (p.Ser54Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at