Variant rs201791791 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001036.6(RYR3):c.13127G>A(p.Arg4376Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000925 in 1,601,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4376W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00093 ( 0 hom. )

Consequence

RYR3
NM_001036.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.79

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]

RYR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009959996).

BP6

Variant 15-33841953-G-A is Benign according to our data. Variant chr15-33841953-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 461859.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33841953-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.13127G>A	p.Arg4376Gln	missense_variant	91/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.13127G>A	p.Arg4376Gln	missense_variant	91/104	1	NM_001036.6	P4	Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.000927

AC:

141

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000736

AC:

168

AN:

228284

Hom.:

AF XY:

0.000851

AC XY:

105

AN XY:

123376

show subpopulations

Gnomad AFR exome

AF:

0.0000741

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.0000599

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000390

Gnomad NFE exome

AF:

0.000988

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.000925

AC:

1341

AN:

1449506

Hom.:

Cov.:

AF XY:

0.000934

AC XY:

672

AN XY:

719702

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000464

Gnomad4 ASJ exome

AF:

0.000349

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.000876

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000751

GnomAD4 genome

AF:

0.000926

AC:

141

AN:

152282

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000954

Hom.:

Bravo

AF:

0.000888

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000265

AC:

ESP6500EA

AF:

0.000731

AC:

ExAC

AF:

0.000845

AC:

102

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 submitter

clinical testing

Invitae

Jul 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.11

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.;.;.;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.010

T;T;T;T;T;T

MetaSVM

Uncertain

0.049

MutationAssessor

Benign

1.5

L;.;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

Polyphen

0.89

P;D;.;.;.;.

Vest4

0.40

MVP

0.88

MPC

0.39

ClinPred

0.059

GERP RS

5.3

Varity_R

0.12

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over