rs182429820

Positions:

• chr15-33624026-A-C
• chr15-33624026-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001036.6(RYR3):​c.2574+3A>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000557 in 1,610,488 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (3 hom.)
• Consequence: RYR3 NM_001036.6 splice_donor_region, intron
• Scores: Splicing: ADA: 0.4816
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.73

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 15-33624026-A-C is Benign according to our data. Variant chr15-33624026-A-C is described in ClinVar as [Benign]. Clinvar id is 461894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.2574+3A>C		splice_donor_region_variant, intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.2574+3A>C		splice_donor_region_variant, intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.2574+3A>C		splice_donor_region_variant, intron_variant		5		A1
RYR3	ENST00000415757.7	c.2574+3A>C		splice_donor_region_variant, intron_variant		2		A2
RYR3	ENST00000634418.1	c.2574+3A>C		splice_donor_region_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00148 AC: 367 AN: 248042 Hom.: 1 AF XY: 0.00140 AC XY: 188 AN XY: 134546

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.0145

Gnomad SAS exome AF: 0.000328

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.000531 AC: 774 AN: 1458110 Hom.: 3 Cov.: 30 AF XY: 0.000531 AC XY: 385 AN XY: 725472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.000430

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000730

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.000807 AC: 123 AN: 152378 Hom.: 0 Cov.: 33 AF XY: 0.00101 AC XY: 75 AN XY: 74514

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000360 Hom.: 0

Bravo AF: 0.000914

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.48
dbscSNV1_RF	Benign	0.59
SpliceAI score (max)		0.62		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.62		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs182429820; hg19: chr15-33916227;