rs2229118

chr15-33623951-T-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001036.6(RYR3):c.2502T>A(p.Ile834=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,613,934 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (592 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (530 hom.)
• Consequence: RYR3 NM_001036.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 15-33623951-T-A is Benign according to our data. Variant chr15-33623951-T-A is described in ClinVar as [Benign]. Clinvar id is 461892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.2502T>A	p.Ile834=	synonymous_variant	20/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.2502T>A	p.Ile834=	synonymous_variant	20/104	1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.2502T>A	p.Ile834=	synonymous_variant	20/104	5		A1
RYR3	ENST00000415757.7	c.2502T>A	p.Ile834=	synonymous_variant	20/103	2		A2
RYR3	ENST00000634418.1	c.2502T>A	p.Ile834=	synonymous_variant	20/102	5

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7332 AN: 152140 Hom.: 588 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0339

GnomAD3 exomes AF: 0.0142 AC: 3529 AN: 249072 Hom.: 232 AF XY: 0.0112 AC XY: 1516 AN XY: 135120

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.00770

Gnomad ASJ exome AF: 0.0417

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000984

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00575 AC: 8409 AN: 1461676 Hom.: 530 Cov.: 32 AF XY: 0.00508 AC XY: 3696 AN XY: 727122

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.00899

Gnomad4 ASJ exome AF: 0.0391

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000451

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0483 AC: 7357 AN: 152258 Hom.: 592 Cov.: 33 AF XY: 0.0450 AC XY: 3347 AN XY: 74454

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0193 Hom.: 47

Bravo AF: 0.0550

Asia WGS AF: 0.00751 AC: 26 AN: 3478

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

Jan 17, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.99
Dann	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs2229118; hg19: chr15-33916152; COSMIC: COSV66802408; COSMIC: COSV66802408;