15-33831331-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.11463+240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,186 control chromosomes in the GnomAD database, including 20,077 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 0.51 (20077 hom., cov: 34)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.11463+240C>T		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.11463+240C>T		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77487 AN: 152068 Hom.: 20037 Cov.: 34

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.510 AC: 77582 AN: 152186 Hom.: 20077 Cov.: 34 AF XY: 0.516 AC XY: 38390 AN XY: 74402

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.502

Alfa AF: 0.467 Hom.: 34118

Bravo AF: 0.505

Asia WGS AF: 0.678 AC: 2355 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.2
Dann	Benign	0.15

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: rs2059956; hg19: chr15-34123532;