chr15-33772101-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
congenital myopathy
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

RYR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.8998A>G	p.Ile3000Val	missense_variant	Exon 63 of 104	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 link	c.8998A>G	p.Ile3000Val	missense_variant	Exon 63 of 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

GnomAD2 exomes

AF:

0.00618

AC:

1539

AN:

248912

AF XY:

0.00464

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 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

African (AFR)

AF:

0.0809

AC:

2708

AN:

33462

American (AMR)

AF:

0.00680

AC:

304

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000302

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.0121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000698

AC:

776

AN:

1111804

Other (OTH)

AF:

0.00656

AC:

396

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

204

409

613

818

1022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0230

AC:

3500

AN:

152190

Hom.:

133

Cov.:

AF XY:

0.0217

AC XY:

1614

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0774

AC:

3213

AN:

41528

American (AMR)

AF:

0.0126

AC:

192

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00125

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68008

Other (OTH)

AF:

0.0133

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00921

Hom.:

119

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

Jan 28, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Epileptic encephalopathy

Benign:1

Nov 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.;.;.

PhyloP100

3.6

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

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr15-33772101-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over