Variant rs10851894 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.8998A>G(p.Ile3000Val) variant causes a missense change. The variant allele was found at a frequency of 0.00482 in 1,613,714 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 133 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 126 hom. )

Consequence

RYR3
NM_001036.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.63

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002326429).

BP6

Variant 15-33772101-A-G is Benign according to our data. Variant chr15-33772101-A-G is described in ClinVar as [Benign]. Clinvar id is 531126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33772101-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.8998A>G	p.Ile3000Val	missense_variant	63/104	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 link	c.8998A>G	p.Ile3000Val	missense_variant	63/104	1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3489

AN:

152072

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00618

AC:

1539

AN:

248912

Hom.:

AF XY:

0.00464

AC XY:

627

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.0775

Gnomad AMR exome

AF:

0.00612

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000850

Gnomad OTH exome

AF:

0.00414

GnomAD4 exome

AF:

0.00293

AC:

4285

AN:

1461524

Hom.:

126

Cov.:

AF XY:

0.00262

AC XY:

1907

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.00680

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000698

Gnomad4 OTH exome

AF:

0.00656

GnomAD4 genome

AF:

0.0230

AC:

3500

AN:

152190

Hom.:

133

Cov.:

AF XY:

0.0217

AC XY:

1614

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0774

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.0268

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0641

AC:

253

ESP6500EA

AF:

0.000361

AC:

ExAC

AF:

0.00739

AC:

894

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00160

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	Jan 28, 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

Aug 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.48

DEOGEN2

Benign

0.25

T;.;.;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;D;D;D;D

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

-0.26

N;N;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.090

.;N;.;.;.

REVEL

Benign

0.27

Sift

Benign

1.0

.;T;.;.;.

Polyphen

0.0010

B;B;.;.;.

Vest4

0.12

MVP

0.45

MPC

0.15

ClinPred

0.018

GERP RS

5.7

Varity_R

0.049

gMVP

0.13

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