15-33821261-T-C

Variant names:

• chr15-33821261-T-C
• rs10714306
• NM_001036.6:c.10816-9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001036.6(RYR3):​c.10816-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,562,504 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (71 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (63 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Scores: Splicing: ADA: 0.00002924
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.106
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-33821261-T-C is Benign according to our data. Variant chr15-33821261-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 461833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

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.10816-9T>C		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.10801-9T>C		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.10816-9T>C		intron	N/A	ENSP00000489262.1
	RYR3	ENST00000389232.9	TSL:5	c.10813-9T>C		intron	N/A	ENSP00000373884.5
	RYR3	ENST00000415757.7	TSL:2	c.10801-9T>C		intron	N/A	ENSP00000399610.3

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2423 AN: 134708 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.00320

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000252

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000726

Gnomad OTH AF: 0.0131

GnomAD2 exomes AF: 0.00429 AC: 854 AN: 199194 AF XY: 0.00338

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.00522

Gnomad ASJ exome AF: 0.00299

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000518

Gnomad OTH exome AF: 0.00446

GnomAD4 exome AF: 0.00197 AC: 2809 AN: 1427710 Hom.: 63 Cov.: 38 AF XY: 0.00178 AC XY: 1259 AN XY: 706858

African (AFR) AF: 0.0558 AC: 1823 AN: 32654

American (AMR) AF: 0.00561 AC: 223 AN: 39760

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 85 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 38092

South Asian (SAS) AF: 0.000123 AC: 10 AN: 81160

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51444

Middle Eastern (MID) AF: 0.00630 AC: 36 AN: 5716

European-Non Finnish (NFE) AF: 0.000363 AC: 397 AN: 1094086

Other (OTH) AF: 0.00394 AC: 234 AN: 59346

GnomAD4 genome AF: 0.0180 AC: 2432 AN: 134794 Hom.: 71 Cov.: 32 AF XY: 0.0170 AC XY: 1111 AN XY: 65534

African (AFR) AF: 0.0628 AC: 2240 AN: 35676

American (AMR) AF: 0.00836 AC: 111 AN: 13270

Ashkenazi Jewish (ASJ) AF: 0.00320 AC: 10 AN: 3122

East Asian (EAS) AF: 0.00 AC: 0 AN: 4532

South Asian (SAS) AF: 0.000252 AC: 1 AN: 3966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9368

Middle Eastern (MID) AF: 0.00407 AC: 1 AN: 246

European-Non Finnish (NFE) AF: 0.000726 AC: 45 AN: 61948

Other (OTH) AF: 0.0129 AC: 24 AN: 1856

Alfa AF: 0.187 Hom.: 5260

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 18, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Epileptic encephalopathy Benign:1

Dec 16, 2024

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs10714306; hg19: chr15-34113462; COSMIC: COSV66805197; COSMIC: COSV66805197;