chr15-33462710-A-G

Variant names:

• chr15-33462710-A-G
• rs2033610
• NM_001036.6:c.52-10709A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001036.6(RYR3):​c.52-10709A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,078 control chromosomes in the GnomAD database, including 26,183 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 0.58 (26183 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.52-10709A>G		intron_variant	Intron 1 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.52-10709A>G		intron_variant	Intron 1 of 103	1	NM_001036.6	ENSP00000489262.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88071 AN: 151960 Hom.: 26147 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.580 AC: 88166 AN: 152078 Hom.: 26183 Cov.: 32 AF XY: 0.577 AC XY: 42879 AN XY: 74336

African (AFR) AF: 0.728 AC: 30203 AN: 41510

American (AMR) AF: 0.546 AC: 8347 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2702 AN: 5170

South Asian (SAS) AF: 0.504 AC: 2424 AN: 4808

European-Finnish (FIN) AF: 0.488 AC: 5155 AN: 10564

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.522 AC: 35484 AN: 67960

Other (OTH) AF: 0.582 AC: 1227 AN: 2108

Alfa AF: 0.539 Hom.: 70387

Bravo AF: 0.595

Asia WGS AF: 0.546 AC: 1898 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	0.0050
DANN	Benign	0.41
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2033610; hg19: chr15-33754911;