Variant 15-33860576-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001036.6(RYR3):c.14300-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,528,146 control chromosomes in the GnomAD database, including 387,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 28876 hom., cov: 30)

Exomes 𝑓: 0.71 ( 358187 hom. )

Consequence

RYR3
NM_001036.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.12

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:

AVEN (HGNC:):

AVEN links:

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

AVEN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 15-33860576-T-A is Benign according to our data. Variant chr15-33860576-T-A is described in ClinVar as [Benign]. Clinvar id is 1257459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.14300-19T>A		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.14300-19T>A		intron_variant		1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86804

AN:

151720

Hom.:

28876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.764

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.745

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.661

AC:

123471

AN:

186662

Hom.:

43269

AF XY:

0.661

AC XY:

65330

AN XY:

98802

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.643

Gnomad EAS exome

AF:

0.395

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.736

Gnomad NFE exome

AF:

0.744

Gnomad OTH exome

AF:

0.662

GnomAD4 exome

AF:

0.712

AC:

980104

AN:

1376306

Hom.:

358187

Cov.:

AF XY:

0.710

AC XY:

484081

AN XY:

681744

show subpopulations

Gnomad4 AFR exome

AF:

0.187

Gnomad4 AMR exome

AF:

0.757

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.394

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.742

Gnomad4 NFE exome

AF:

0.750

Gnomad4 OTH exome

AF:

0.664

GnomAD4 genome

AF:

0.572

AC:

86813

AN:

151840

Hom.:

28876

Cov.:

AF XY:

0.574

AC XY:

42555

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.646

Gnomad4 EAS

AF:

0.405

Gnomad4 SAS

AF:

0.563

Gnomad4 FIN

AF:

0.725

Gnomad4 NFE

AF:

0.745

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.659

Hom.:

6348

Bravo

AF:

0.552

Asia WGS

AF:

0.476

AC:

1657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 04, 2019	- -
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

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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