15-33625741-T-C

Position:

• chr15-33625741-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001036.6(RYR3):​c.2574+1718T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,872 control chromosomes in the GnomAD database, including 12,657 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 0.40 (12657 hom., cov: 31)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.2574+1718T>C		intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.2574+1718T>C		intron_variant		1	NM_001036.6	ENSP00000489262.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60954 AN: 151752 Hom.: 12647 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.402 AC: 60998 AN: 151872 Hom.: 12657 Cov.: 31 AF XY: 0.408 AC XY: 30257 AN XY: 74230

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.381

Alfa AF: 0.407 Hom.: 7696

Bravo AF: 0.396

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.56

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: rs951442; hg19: chr15-33917942;