15-33662923-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001036.6(RYR3):​c.5393G>C​(p.Arg1798Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RYR3
NM_001036.6 missense

Scores

10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR3NM_001036.6 linkc.5393G>C p.Arg1798Pro missense_variant Exon 35 of 104 ENST00000634891.2 NP_001027.3 Q15413-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYR3ENST00000634891.2 linkc.5393G>C p.Arg1798Pro missense_variant Exon 35 of 104 1 NM_001036.6 ENSP00000489262.1 Q15413-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
D;.;.;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D;D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.68
D;D;D;D;D
MetaSVM
Benign
-0.48
T
MutationAssessor
Benign
1.9
L;L;.;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.8
.;D;D;.;.
REVEL
Benign
0.24
Sift
Benign
0.067
.;T;T;.;.
Polyphen
0.92
P;D;.;.;.
Vest4
0.76
MutPred
0.33
Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP
0.72
MPC
0.43
ClinPred
0.92
D
GERP RS
5.0
Varity_R
0.55
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-33955124; API