chr15-33788936-G-A

Variant names:

• chr15-33788936-G-A
• rs965471
• NM_001036.6:c.9830+478G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001036.6(RYR3):​c.9830+478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,022 control chromosomes in the GnomAD database, including 29,721 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 0.61 (29721 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 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.9830+478G>A		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.9830+478G>A		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.9830+478G>A		intron	N/A	ENSP00000489262.1
	RYR3	ENST00000389232.9	TSL:5	c.9827+478G>A		intron	N/A	ENSP00000373884.5
	RYR3	ENST00000415757.7	TSL:2	c.9830+478G>A		intron	N/A	ENSP00000399610.3

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93235 AN: 151904 Hom.: 29718 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.614 AC: 93281 AN: 152022 Hom.: 29721 Cov.: 32 AF XY: 0.622 AC XY: 46237 AN XY: 74326

African (AFR) AF: 0.461 AC: 19093 AN: 41440

American (AMR) AF: 0.559 AC: 8545 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2278 AN: 3470

East Asian (EAS) AF: 0.958 AC: 4951 AN: 5170

South Asian (SAS) AF: 0.807 AC: 3891 AN: 4824

European-Finnish (FIN) AF: 0.741 AC: 7826 AN: 10566

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44648 AN: 67962

Other (OTH) AF: 0.647 AC: 1365 AN: 2110

Alfa AF: 0.644 Hom.: 10208

Bravo AF: 0.589

Asia WGS AF: 0.856 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		0.017
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: rs965471; hg19: chr15-34081137;