rs182429820

Variant names:

• chr15-33624026-A-C
• rs182429820
• NM_001036.6:c.2574+3A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001036.6(RYR3):​c.2574+3A>C variant causes a splice 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. 2/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.4816
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.73
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 461894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001036.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3	NM_001036.6	MANE Select	c.2574+3A>C		splice_region intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.2574+3A>C		splice_region intron	N/A	NP_001230925.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3	ENST00000634891.2	TSL:1 MANE Select	c.2574+3A>C		splice_region intron	N/A	ENSP00000489262.1
	RYR3	ENST00000389232.9	TSL:5	c.2574+3A>C		splice_region intron	N/A	ENSP00000373884.5
	RYR3	ENST00000415757.7	TSL:2	c.2574+3A>C		splice_region intron	N/A	ENSP00000399610.3

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

GnomAD2 exomes AF: 0.00148 AC: 367 AN: 248042 AF XY: 0.00140

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33344

American (AMR) AF: 0.00141 AC: 63 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26074

East Asian (EAS) AF: 0.0122 AC: 483 AN: 39678

South Asian (SAS) AF: 0.000430 AC: 37 AN: 86070

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.0000730 AC: 81 AN: 1109126

Other (OTH) AF: 0.00111 AC: 67 AN: 60250

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

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.00216 AC: 33 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5190

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

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

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		5.7
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs182429820; hg19: chr15-33916227;