rs2596156

Variant names:

• chr15-33449977-C-T
• rs2596156
• NM_001036.6:c.52-23442C>T

Variant summary

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

The NM_001036.6(RYR3):​c.52-23442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,664 control chromosomes in the GnomAD database, including 34,684 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 0.67 (34684 hom., cov: 28)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.52-23442C>T		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.52-23442C>T		intron_variant	Intron 1 of 103	1	NM_001036.6	ENSP00000489262.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101010 AN: 151548 Hom.: 34632 Cov.: 28

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.667 AC: 101119 AN: 151664 Hom.: 34684 Cov.: 28 AF XY: 0.669 AC XY: 49550 AN XY: 74100

African (AFR) AF: 0.856 AC: 35418 AN: 41384

American (AMR) AF: 0.617 AC: 9386 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2112 AN: 3468

East Asian (EAS) AF: 0.585 AC: 3009 AN: 5142

South Asian (SAS) AF: 0.588 AC: 2807 AN: 4774

European-Finnish (FIN) AF: 0.656 AC: 6893 AN: 10502

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39304 AN: 67876

Other (OTH) AF: 0.659 AC: 1383 AN: 2100

Alfa AF: 0.600 Hom.: 14250

Bravo AF: 0.676

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-0.37
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: rs2596156; hg19: chr15-33742178;