Variant rs114681942 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.11876T>C(p.Ile3959Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000111 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

RYR3
NM_001036.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.04

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=0.02012083).

BP6

Variant 15-33837856-T-C is Benign according to our data. Variant chr15-33837856-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 461847.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.11876T>C	p.Ile3959Thr	missense_variant	89/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.11876T>C	p.Ile3959Thr	missense_variant	89/104	1	NM_001036.6	P4	Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000201

AC:

AN:

249066

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.00187

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000746

AC:

109

AN:

1461708

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.000157

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:

0.0000288

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000460

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000875

Hom.:

Bravo

AF:

0.000559

ESP6500AA

AF:

0.00129

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000248

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

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

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

D;.;.;.;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.020

T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.98

L;.;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

.;D;.;.;.

REVEL

Uncertain

0.57

Sift

Benign

0.16

.;T;.;.;.

Polyphen

0.12

B;D;.;.;.

Vest4

0.53

MVP

0.74

MPC

0.24

ClinPred

0.033

GERP RS

5.4

Varity_R

0.33

gMVP

0.55

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