rs61996335
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001036.6(RYR3):c.9254C>G(p.Pro3085Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00399 in 1,613,820 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001036.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00298 AC: 453AN: 152198Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00281 AC: 699AN: 248350Hom.: 1 AF XY: 0.00284 AC XY: 382AN XY: 134726
GnomAD4 exome AF: 0.00409 AC: 5979AN: 1461504Hom.: 18 Cov.: 31 AF XY: 0.00398 AC XY: 2893AN XY: 727028
GnomAD4 genome AF: 0.00297 AC: 453AN: 152316Hom.: 3 Cov.: 32 AF XY: 0.00255 AC XY: 190AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
RYR3 NM_001036.4 exon 65 p.Pro3085Arg (c.9254C>G): This variant has not been reported in the literature but is present in 0.5% (372/68026) of European alleles including 3 homozygotes in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/15-33780327-C-G?dataset=gnomad_r3). This variant is present in ClinVar classified as a benign variant (Variation ID:461984). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore, the clinical significance of this variant is uncertain. -
RYR3: BP4, BS2 -
Epileptic encephalopathy Benign:1
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RYR3-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at