Variant rs61996336 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001036.6(RYR3):c.9816C>T(p.Tyr3272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,613,704 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 39 hom., cov: 33)

Exomes 𝑓: 0.025 ( 569 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.16

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]

RYR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 15-33788444-C-T is Benign according to our data. Variant chr15-33788444-C-T is described in ClinVar as [Benign]. Clinvar id is 461991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0171 (2609/152322) while in subpopulation NFE AF= 0.0289 (1966/68028). AF 95% confidence interval is 0.0278. There are 39 homozygotes in gnomad4. There are 1198 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.9816C>T	p.Tyr3272=	synonymous_variant	67/104	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.9816C>T	p.Tyr3272=	synonymous_variant	67/104	1	NM_001036.6	ENSP00000489262	P4	Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2611

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.00857

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0156

AC:

3870

AN:

248424

Hom.:

AF XY:

0.0157

AC XY:

2121

AN XY:

134856

show subpopulations

Gnomad AFR exome

AF:

0.00452

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.00832

Gnomad NFE exome

AF:

0.0246

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0250

AC:

36535

AN:

1461382

Hom.:

569

Cov.:

AF XY:

0.0245

AC XY:

17794

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00382

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0191

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00643

Gnomad4 FIN exome

AF:

0.00888

Gnomad4 NFE exome

AF:

0.0297

Gnomad4 OTH exome

AF:

0.0217

GnomAD4 genome

AF:

0.0171

AC:

2609

AN:

152322

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1198

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00517

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.00857

Gnomad4 NFE

AF:

0.0289

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0222

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0273

EpiControl

AF:

0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

RYR3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2020

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

1.1

DANN

Benign

0.48

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