NM_001036.6:c.6619+6859G>C

Variant names:

• chr15-33713913-G-C
• rs62012610
• NM_001036.6:c.6619+6859G>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.6619+6859G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 152,186 control chromosomes in the GnomAD database, including 471 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 0.057 (471 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001036.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3	NM_001036.6	MANE Select	c.6619+6859G>C		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.6619+6859G>C		intron	N/A	NP_001230925.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3	ENST00000634891.2	TSL:1 MANE Select	c.6619+6859G>C		intron	N/A	ENSP00000489262.1
	RYR3	ENST00000389232.9	TSL:5	c.6619+6859G>C		intron	N/A	ENSP00000373884.5
	RYR3	ENST00000415757.7	TSL:2	c.6619+6859G>C		intron	N/A	ENSP00000399610.3

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8657 AN: 152068 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0538

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

GnomAD4 genome AF: 0.0569 AC: 8656 AN: 152186 Hom.: 471 Cov.: 32 AF XY: 0.0589 AC XY: 4381 AN XY: 74392

African (AFR) AF: 0.0153 AC: 636 AN: 41538

American (AMR) AF: 0.0426 AC: 651 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1285 AN: 5156

South Asian (SAS) AF: 0.222 AC: 1067 AN: 4812

European-Finnish (FIN) AF: 0.0196 AC: 208 AN: 10608

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0633 AC: 4302 AN: 68006

Other (OTH) AF: 0.0537 AC: 113 AN: 2104

Alfa AF: 0.0207 Hom.: 11

Bravo AF: 0.0534

Asia WGS AF: 0.186 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.43
PhyloP100		-0.84
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: rs62012610; hg19: chr15-34006114;