NM_001036.6:c.8817-993T>C

Variant names:

• chr15-33770927-T-C
• rs7497692
• NM_001036.6:c.8817-993T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
• congenital myopathy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.8817-993T>C		intron_variant	Intron 62 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.8817-993T>C		intron_variant	Intron 62 of 103	1	NM_001036.6	ENSP00000489262.1

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

African (AFR) AF: 0.0824 AC: 3423 AN: 41564

American (AMR) AF: 0.170 AC: 2605 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3468

East Asian (EAS) AF: 0.165 AC: 855 AN: 5170

South Asian (SAS) AF: 0.279 AC: 1347 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2438 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14609 AN: 67988

Other (OTH) AF: 0.195 AC: 412 AN: 2116

Alfa AF: 0.205 Hom.: 11776

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
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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