dbSNP rs2291734: RYR3:c.3382-77G>A (chr15-33636299-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001036.6(RYR3):c.3382-77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,266,648 control chromosomes in the GnomAD database, including 25,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2279 hom., cov: 32)

Exomes 𝑓: 0.20 ( 23046 hom. )

Consequence

RYR3
NM_001036.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.711

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.3382-77G>A		intron_variant	Intron 26 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
RYR3	ENST00000634891.2 link	c.3382-77G>A	intron_variant	Intron 26 of 103	1	NM_001036.6	ENSP00000489262.1
RYR3	ENST00000389232.9 link	c.3382-77G>A	intron_variant	Intron 26 of 103	5		ENSP00000373884.5
RYR3	ENST00000415757.7 link	c.3382-77G>A	intron_variant	Intron 26 of 102	2		ENSP00000399610.3
RYR3	ENST00000634418.1 link	c.3382-77G>A	intron_variant	Intron 26 of 101	5		ENSP00000489529.1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23627

AN:

151890

Hom.:

2274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0427

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.198

AC:

220512

AN:

1114640

Hom.:

23046

AF XY:

0.199

AC XY:

113152

AN XY:

569870

show subpopulations

African (AFR)

AF:

0.0356

AC:

921

AN:

25902

American (AMR)

AF:

0.288

AC:

11421

AN:

39620

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

2625

AN:

22294

East Asian (EAS)

AF:

0.169

AC:

6434

AN:

38126

South Asian (SAS)

AF:

0.240

AC:

18045

AN:

75088

European-Finnish (FIN)

AF:

0.226

AC:

11831

AN:

52446

Middle Eastern (MID)

AF:

0.153

AC:

723

AN:

4718

European-Non Finnish (NFE)

AF:

0.198

AC:

159914

AN:

807910

Other (OTH)

AF:

0.177

AC:

8598

AN:

48536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8906

17813

26719

35626

44532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4948

9896

14844

19792

24740

<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:

0.156

AC:

23652

AN:

152008

Hom.:

2279

Cov.:

AF XY:

0.159

AC XY:

11847

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0427

AC:

1771

AN:

41474

American (AMR)

AF:

0.231

AC:

3521

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

390

AN:

3462

East Asian (EAS)

AF:

0.132

AC:

682

AN:

5162

South Asian (SAS)

AF:

0.234

AC:

1126

AN:

4806

European-Finnish (FIN)

AF:

0.224

AC:

2366

AN:

10568

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13243

AN:

67968

Other (OTH)

AF:

0.151

AC:

318

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

973

1946

2918

3891

4864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.179

Hom.:

7901

Bravo

AF:

0.148

Asia WGS

AF:

0.200

AC:

697

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.90

(source)

DANN

Benign

0.46

PhyloP100

-0.71

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

Computational scores

Splicing

Publications

Other links and lift over