rs201524472

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001036.6(RYR3):ā€‹c.5524A>Cā€‹(p.Lys1842Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000186 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00014 ( 0 hom., cov: 32)
Exomes š‘“: 0.00019 ( 0 hom. )

Consequence

RYR3
NM_001036.6 missense

Scores

2
7
6

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.16
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;
BP6
Variant 15-33663642-A-C is Benign according to our data. Variant chr15-33663642-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 461930.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RYR3NM_001036.6 linkuse as main transcriptc.5524A>C p.Lys1842Gln missense_variant 36/104 ENST00000634891.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RYR3ENST00000634891.2 linkuse as main transcriptc.5524A>C p.Lys1842Gln missense_variant 36/1041 NM_001036.6 P4Q15413-1
RYR3ENST00000389232.9 linkuse as main transcriptc.5524A>C p.Lys1842Gln missense_variant 36/1045 A1
RYR3ENST00000415757.7 linkuse as main transcriptc.5524A>C p.Lys1842Gln missense_variant 36/1032 A2Q15413-2
RYR3ENST00000634418.1 linkuse as main transcriptc.5524A>C p.Lys1842Gln missense_variant 36/1025

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000190
AC:
47
AN:
247970
Hom.:
0
AF XY:
0.000201
AC XY:
27
AN XY:
134504
show subpopulations
Gnomad AFR exome
AF:
0.0000651
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000372
Gnomad NFE exome
AF:
0.000320
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000191
AC:
279
AN:
1461066
Hom.:
0
Cov.:
31
AF XY:
0.000183
AC XY:
133
AN XY:
726716
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.000318
Gnomad4 NFE exome
AF:
0.000231
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000275
Hom.:
0
Bravo
AF:
0.000147
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000238
AC:
2
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.000600
EpiControl
AF:
0.0000595

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 16, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
T;.;.;.;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.49
T;T;T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Benign
1.9
L;L;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
Polyphen
0.99
D;P;.;.;.
Vest4
0.75
MVP
0.72
MPC
0.24
ClinPred
0.072
T
GERP RS
5.3
Varity_R
0.30
gMVP
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201524472; hg19: chr15-33955843; API