chr15-33362416-G-T

Position:

• chr15-33362416-G-T

Variant summary

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

The NM_001036.6(RYR3):​c.51+51320G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 149,128 control chromosomes in the GnomAD database, including 20,548 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 0.52 (20548 hom., cov: 27)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.51+51320G>T		intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.51+51320G>T		intron_variant		1	NM_001036.6	ENSP00000489262	P4

Frequencies

GnomAD3 genomes AF: 0.524 AC: 78147 AN: 149014 Hom.: 20538 Cov.: 27

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.524 AC: 78205 AN: 149128 Hom.: 20548 Cov.: 27 AF XY: 0.524 AC XY: 38143 AN XY: 72800

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.494

Alfa AF: 0.422 Hom.: 1254

Bravo AF: 0.515

Asia WGS AF: 0.560 AC: 1946 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.46

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: rs2676035; hg19: chr15-33654617; COSMIC: COSV66809228;