Variant rs73372074 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001036.6(RYR3):c.12558C>G(p.Ser4186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,862 control chromosomes in the GnomAD database, including 1,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. S4186S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.046 ( 420 hom., cov: 32)

Exomes 𝑓: 0.011 ( 729 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 15-33838538-C-G is Benign according to our data. Variant chr15-33838538-C-G is described in ClinVar as [Benign]. Clinvar id is 461853.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.12558C>G	p.Ser4186=	synonymous_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.12558C>G	p.Ser4186=	synonymous_variant	89/104	1	NM_001036.6	P4	Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6932

AN:

152082

Hom.:

420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0722

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0220

AC:

5482

AN:

249014

Hom.:

271

AF XY:

0.0223

AC XY:

3013

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0707

Gnomad FIN exome

AF:

0.00297

Gnomad NFE exome

AF:

0.00336

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0112

AC:

16376

AN:

1461662

Hom.:

729

Cov.:

AF XY:

0.0125

AC XY:

9076

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0690

Gnomad4 FIN exome

AF:

0.00272

Gnomad4 NFE exome

AF:

0.00251

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0456

AC:

6940

AN:

152200

Hom.:

420

Cov.:

AF XY:

0.0454

AC XY:

3376

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.00312

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0503

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.21

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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