rs41279202

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001036.6(RYR3):c.855A>T(p.Arg285Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,613,722 control chromosomes in the GnomAD database, including 1,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 99 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1323 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.28

Publications

7 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=-0.56).

BP6

Variant 15-33550199-A-T is Benign according to our data. Variant chr15-33550199-A-T is described in ClinVar as Benign. ClinVar VariationId is 461971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0304 (4633/152268) while in subpopulation NFE AF = 0.045 (3064/68018). AF 95% confidence interval is 0.0437. There are 99 homozygotes in GnomAd4. There are 2165 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 99 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.855A>T	p.Arg285Arg	synonymous_variant	Exon 10 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.855A>T	p.Arg285Arg	synonymous_variant	Exon 10 of 104	1	NM_001036.6	ENSP00000489262.1	Q15413-1
RYR3	ENST00000389232.9 link	c.855A>T	p.Arg285Arg	synonymous_variant	Exon 10 of 104	5		ENSP00000373884.5	A0A0X1KG73
RYR3	ENST00000415757.7 link	c.855A>T	p.Arg285Arg	synonymous_variant	Exon 10 of 103	2		ENSP00000399610.3	Q15413-2
RYR3	ENST00000634418.1 link	c.855A>T	p.Arg285Arg	synonymous_variant	Exon 10 of 102	5		ENSP00000489529.1	A0A0U1RRH1

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4634

AN:

152150

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0312

AC:

7759

AN:

248576

AF XY:

0.0319

show subpopulations

Gnomad AFR exome

AF:

0.00734

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0789

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0428

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0402

AC:

58786

AN:

1461454

Hom.:

1323

Cov.:

AF XY:

0.0399

AC XY:

29015

AN XY:

726978

show subpopulations

African (AFR)

AF:

0.00732

AC:

245

AN:

33478

American (AMR)

AF:

0.0175

AC:

783

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0797

AC:

2083

AN:

26128

East Asian (EAS)

AF:

0.000126

AC:

AN:

39682

South Asian (SAS)

AF:

0.0160

AC:

1383

AN:

86216

European-Finnish (FIN)

AF:

0.0359

AC:

1916

AN:

53386

Middle Eastern (MID)

AF:

0.0348

AC:

201

AN:

5768

European-Non Finnish (NFE)

AF:

0.0449

AC:

49954

AN:

1111716

Other (OTH)

AF:

0.0367

AC:

2216

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2821

5642

8463

11284

14105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1834

3668

5502

7336

9170

<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:

0.0304

AC:

4633

AN:

152268

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

2165

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00847

AC:

352

AN:

41554

American (AMR)

AF:

0.0243

AC:

371

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

294

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.0166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0342

AC:

362

AN:

10598

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0450

AC:

3064

AN:

68018

Other (OTH)

AF:

0.0279

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

234

468

702

936

1170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0447

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0468

EpiControl

AF:

0.0423

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Jan 15, 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

-0.56

CADD

Benign

3.8

(source)

DANN

Benign

0.60

PhyloP100

-1.3

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