15-33623951-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001036.6(RYR3):c.2502T>A(p.Ile834Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,613,934 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 592 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 530 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

Publications

2 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 15-33623951-T-A is Benign according to our data. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33623951-T-A is described in CliVar as Benign. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.2502T>A	p.Ile834Ile	synonymous_variant	Exon 20 of 104	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR3	ENST00000634891.2 link	c.2502T>A	p.Ile834Ile	synonymous_variant	Exon 20 of 104	1	NM_001036.6	ENSP00000489262.1	Q15413-1
RYR3	ENST00000389232.9 link	c.2502T>A	p.Ile834Ile	synonymous_variant	Exon 20 of 104	5		ENSP00000373884.5	A0A0X1KG73
RYR3	ENST00000415757.7 link	c.2502T>A	p.Ile834Ile	synonymous_variant	Exon 20 of 103	2		ENSP00000399610.3	Q15413-2
RYR3	ENST00000634418.1 link	c.2502T>A	p.Ile834Ile	synonymous_variant	Exon 20 of 102	5		ENSP00000489529.1	A0A0U1RRH1

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

7332

AN:

152140

Hom.:

588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0142

AC:

3529

AN:

249072

AF XY:

0.0112

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.00770

Gnomad ASJ exome

AF:

0.0417

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000984

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00575

AC:

8409

AN:

1461676

Hom.:

530

Cov.:

AF XY:

0.00508

AC XY:

3696

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.169

AC:

5664

AN:

33480

American (AMR)

AF:

0.00899

AC:

402

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0391

AC:

1023

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000278

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000451

AC:

501

AN:

1111840

Other (OTH)

AF:

0.0128

AC:

772

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

411

822

1232

1643

2054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0483

AC:

7357

AN:

152258

Hom.:

592

Cov.:

AF XY:

0.0450

AC XY:

3347

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.164

AC:

6822

AN:

41508

American (AMR)

AF:

0.0169

AC:

259

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000809

AC:

AN:

68018

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

298

596

895

1193

1491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0550

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.99

(source)

DANN

Benign

0.64

PhyloP100

-1.1

Mutation Taster

=100/0

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

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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