Variant rs115119086 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001036.6(RYR3):c.4701G>A(p.Ala1567Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,609,062 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.44

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:

RYR3 (HGNC:):

RYR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 15-33662231-G-A is Benign according to our data. Variant chr15-33662231-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 461917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.4701G>A	p.Ala1567Ala	synonymous_variant	35/104	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.4701G>A	p.Ala1567Ala	synonymous_variant	35/104	1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

396

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00803

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.000367

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.000902

AC:

215

AN:

238370

Hom.:

AF XY:

0.000751

AC XY:

AN XY:

129128

show subpopulations

Gnomad AFR exome

AF:

0.00896

Gnomad AMR exome

AF:

0.000478

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000690

Gnomad FIN exome

AF:

0.0000964

Gnomad NFE exome

AF:

0.000566

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.000482

AC:

702

AN:

1456728

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

310

AN XY:

724046

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.000545

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0000755

Gnomad4 NFE exome

AF:

0.000252

Gnomad4 OTH exome

AF:

0.000897

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152334

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00813

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00339

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	RYR3: BP4, BP7 -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

RYR3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 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

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.15

DANN

Benign

0.51

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