chr15-33770927-T-C

Position:

• chr15-33770927-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.8817-993T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,210 control chromosomes in the GnomAD database, including 2,609 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 0.18 (2609 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.8817-993T>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.8817-993T>C		intron_variant		1	NM_001036.6	ENSP00000489262	P4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26746 AN: 152092 Hom.: 2611 Cov.: 33

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.176 AC: 26735 AN: 152210 Hom.: 2609 Cov.: 33 AF XY: 0.178 AC XY: 13223 AN XY: 74418

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.195

Alfa AF: 0.214 Hom.: 5554

Bravo AF: 0.164

Asia WGS AF: 0.224 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.58
DANN	Benign	0.70

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: rs7497692; hg19: chr15-34063128; COSMIC: COSV66809694;