dbSNP rs1495280: RYR3:c.3176-51C>T (chr15-33635563-C-T) – 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.3176-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,405,366 control chromosomes in the GnomAD database, including 168,667 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 0.52 ( 20673 hom., cov: 32)

Exomes 𝑓: 0.48 ( 147994 hom. )

Consequence

RYR3
NM_001036.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

9 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.3176-51C>T		intron_variant	Intron 25 of 103	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR3	ENST00000634891.2 link	c.3176-51C>T	intron_variant	Intron 25 of 103	1	NM_001036.6	ENSP00000489262.1	Q15413-1
RYR3	ENST00000389232.9 link	c.3176-51C>T	intron_variant	Intron 25 of 103	5		ENSP00000373884.5	A0A0X1KG73
RYR3	ENST00000415757.7 link	c.3176-51C>T	intron_variant	Intron 25 of 102	2		ENSP00000399610.3	Q15413-2
RYR3	ENST00000634418.1 link	c.3176-51C>T	intron_variant	Intron 25 of 101	5		ENSP00000489529.1	A0A0U1RRH1

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78409

AN:

151960

Hom.:

20631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.483

AC:

605084

AN:

1253288

Hom.:

147994

Cov.:

AF XY:

0.482

AC XY:

303680

AN XY:

629734

show subpopulations

African (AFR)

AF:

0.586

AC:

17353

AN:

29590

American (AMR)

AF:

0.634

AC:

24979

AN:

39414

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

9784

AN:

24418

East Asian (EAS)

AF:

0.656

AC:

24874

AN:

37912

South Asian (SAS)

AF:

0.528

AC:

41420

AN:

78426

European-Finnish (FIN)

AF:

0.530

AC:

27289

AN:

51480

Middle Eastern (MID)

AF:

0.452

AC:

2345

AN:

5192

European-Non Finnish (NFE)

AF:

0.462

AC:

430926

AN:

933448

Other (OTH)

AF:

0.489

AC:

26114

AN:

53408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16700

33400

50099

66799

83499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12394

24788

37182

49576

61970

<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:

0.516

AC:

78512

AN:

152078

Hom.:

20673

Cov.:

AF XY:

0.518

AC XY:

38514

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.586

AC:

24340

AN:

41504

American (AMR)

AF:

0.552

AC:

8436

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1371

AN:

3468

East Asian (EAS)

AF:

0.662

AC:

3416

AN:

5164

South Asian (SAS)

AF:

0.522

AC:

2518

AN:

4824

European-Finnish (FIN)

AF:

0.524

AC:

5534

AN:

10554

Middle Eastern (MID)

AF:

0.432

AC:

126

AN:

292

European-Non Finnish (NFE)

AF:

0.459

AC:

31211

AN:

67968

Other (OTH)

AF:

0.490

AC:

1031

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1937

3875

5812

7750

9687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.475

Hom.:

65288

Bravo

AF:

0.523

Asia WGS

AF:

0.622

AC:

2162

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.3

(source)

DANN

Benign

0.60

PhyloP100

1.8

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