rs553354987

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001036.6(RYR3):​c.4483A>C​(p.Ile1495Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,410,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

RYR3
NM_001036.6 missense

Scores

1
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23567164).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR3NM_001036.6 linkc.4483A>C p.Ile1495Leu missense_variant Exon 34 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.4483A>C p.Ile1495Leu missense_variant Exon 34 of 104 1 NM_001036.6 ENSP00000489262.1 Q15413-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000142
AC:
2
AN:
1410894
Hom.:
0
Cov.:
32
AF XY:
0.00000143
AC XY:
1
AN XY:
696900
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Benign
19
DANN
Benign
0.82
DEOGEN2
Benign
0.26
T;.;.;.;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.17
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.84
T;T;T;T;T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
-0.35
N;N;.;.;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
0.36
.;N;N;.;.
REVEL
Uncertain
0.48
Sift
Benign
1.0
.;T;T;.;.
Polyphen
0.017
B;B;.;.;.
Vest4
0.47
MutPred
0.42
Loss of catalytic residue at P1497 (P = 0.0333);Loss of catalytic residue at P1497 (P = 0.0333);Loss of catalytic residue at P1497 (P = 0.0333);Loss of catalytic residue at P1497 (P = 0.0333);Loss of catalytic residue at P1497 (P = 0.0333);
MVP
0.69
MPC
0.18
ClinPred
0.76
D
GERP RS
4.8
Varity_R
0.19
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr15-33952485; API