rs753191794
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001036.6(RYR3):c.808C>T(p.Arg270Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,608,458 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
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
RYR3
NM_001036.6 missense
NM_001036.6 missense
Scores
14
2
2
Clinical Significance
Conservation
PhyloP100: 1.05
Genes affected
RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.937
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.808C>T | p.Arg270Trp | missense_variant | 9/104 | ENST00000634891.2 | NP_001027.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.808C>T | p.Arg270Trp | missense_variant | 9/104 | 1 | NM_001036.6 | ENSP00000489262.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000817 AC: 2AN: 244770Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132554
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1456272Hom.: 0 Cov.: 29 AF XY: 0.0000152 AC XY: 11AN XY: 724450
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 26, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;D;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;.;.
Polyphen
D;D;.;.;.
Vest4
MVP
0.93
MPC
0.74
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at