Variant 15-33826703-G-A 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.11196G>A(p.Thr3732Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,613,924 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 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.293

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 15-33826703-G-A is Benign according to our data. Variant chr15-33826703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 461838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.293 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 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.11196G>A	p.Thr3732Thr	synonymous_variant	84/104	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.11196G>A	p.Thr3732Thr	synonymous_variant	84/104	1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

230

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00933

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00185

AC:

461

AN:

249216

Hom.:

AF XY:

0.00203

AC XY:

274

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.00961

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.00110

AC:

1607

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

870

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00852

Gnomad4 NFE exome

AF:

0.000749

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00150

AC:

229

AN:

152276

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00933

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.000586

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00130

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	RYR3: BP4, BP7 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.5

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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