rs2596156

Positions:

• chr15-33449977-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
RYR3	NM_001036.6	c.52-23442C>T		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.52-23442C>T		intron_variant		1	NM_001036.6	P4

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

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.659

Alfa AF: 0.599 Hom.: 12627

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

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: rs2596156; hg19: chr15-33742178;