Variant rs202244063 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001036.6(RYR3):c.1295T>G(p.Ile432Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000613 in 1,612,494 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 6 hom. )

Consequence

RYR3
NM_001036.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.14

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040059686).

BP6

Variant 15-33580002-T-G is Benign according to our data. Variant chr15-33580002-T-G is described in ClinVar as [Benign]. Clinvar id is 461857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.1295T>G	p.Ile432Ser	missense_variant	13/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.1295T>G	p.Ile432Ser	missense_variant	13/104	1	NM_001036.6	P4	Q15413-1
RYR3	ENST00000389232.9 linkuse as main transcript	c.1295T>G	p.Ile432Ser	missense_variant	13/104	5		A1
RYR3	ENST00000415757.7 linkuse as main transcript	c.1295T>G	p.Ile432Ser	missense_variant	13/103	2		A2	Q15413-2
RYR3	ENST00000634418.1 linkuse as main transcript	c.1295T>G	p.Ile432Ser	missense_variant	13/102	5

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

514

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000893

AC:

221

AN:

247606

Hom.:

AF XY:

0.000581

AC XY:

AN XY:

134306

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.000674

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000502

GnomAD4 exome

AF:

0.000323

AC:

471

AN:

1460394

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.000651

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000796

GnomAD4 genome

AF:

0.00340

AC:

517

AN:

152100

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

205

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000621

Hom.:

Bravo

AF:

0.00395

ESP6500AA

AF:

0.0142

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00107

AC:

129

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 01, 2023

- -

RYR3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.32

T;.;.;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.47

T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.8

L;L;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

.;N;N;.;.

REVEL

Uncertain

0.30

Sift

Benign

0.47

.;T;T;.;.

Polyphen

0.011

B;B;.;.;.

Vest4

0.11

MVP

0.44

MPC

0.26

ClinPred

0.024

GERP RS

5.2

Varity_R

0.20

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.

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