Variant rs182429820 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001036.6(RYR3):c.2574+3A>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000557 in 1,610,488 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 3 hom. )

Consequence

RYR3
NM_001036.6 splice_region, intron

Scores

Splicing: ADA: 0.4816

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.73

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 15-33624026-A-C is Benign according to our data. Variant chr15-33624026-A-C is described in ClinVar as [Benign]. Clinvar id is 461894.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.2574+3A>C		splice_region_variant, intron_variant		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.2574+3A>C		splice_region_variant, intron_variant		1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00148

AC:

367

AN:

248042

Hom.:

AF XY:

0.00140

AC XY:

188

AN XY:

134546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000125

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.000531

AC:

774

AN:

1458110

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

385

AN XY:

725472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0122

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000730

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000807

AC:

123

AN:

152378

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000914

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.48

dbscSNV1_RF

Benign

0.59

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.62

Position offset: -3

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