15-33647294-C-T

Position:

• chr15-33647294-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.3942-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 678,702 control chromosomes in the GnomAD database, including 16,812 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 0.21 (3331 hom., cov: 32)
  • Exomes 𝑓: 0.22 (13481 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.3942-130C>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.3942-130C>T		intron_variant		1	NM_001036.6	ENSP00000489262	P4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31355 AN: 152022 Hom.: 3334 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.219 AC: 115362 AN: 526562 Hom.: 13481 AF XY: 0.221 AC XY: 62161 AN XY: 281230

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.206 AC: 31356 AN: 152140 Hom.: 3331 Cov.: 32 AF XY: 0.205 AC XY: 15262 AN XY: 74372

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.231

Alfa AF: 0.220 Hom.: 5493

Bravo AF: 0.205

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.69

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: rs2291736; hg19: chr15-33939495; COSMIC: COSV66782201;