NM_001036.6:c.11463+240C>T

Variant names:

• chr15-33831331-C-T
• rs2059956
• NM_001036.6:c.11463+240C>T

Variant summary

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

The NM_001036.6(RYR3):​c.11463+240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,186 control chromosomes in the GnomAD database, including 20,077 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 0.51 (20077 hom., cov: 34)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• Publications: 4 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: G2P, PanelApp Australia, ClinGen
• congenital myopathy

  Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3	NM_001036.6	MANE Select	c.11463+240C>T		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.11448+240C>T		intron	N/A	NP_001230925.1	Q15413-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RYR3	ENST00000634891.2	TSL:1 MANE Select	c.11463+240C>T		intron	N/A	ENSP00000489262.1	Q15413-1
	RYR3	ENST00000389232.9	TSL:5	c.11460+240C>T		intron	N/A	ENSP00000373884.5	A0A0X1KG73
	RYR3	ENST00000415757.7	TSL:2	c.11448+240C>T		intron	N/A	ENSP00000399610.3	Q15413-2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77487 AN: 152068 Hom.: 20037 Cov.: 34

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.510 AC: 77582 AN: 152186 Hom.: 20077 Cov.: 34 AF XY: 0.516 AC XY: 38390 AN XY: 74402

African (AFR) AF: 0.553 AC: 22969 AN: 41514

American (AMR) AF: 0.524 AC: 8019 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3691 AN: 5180

South Asian (SAS) AF: 0.689 AC: 3328 AN: 4830

European-Finnish (FIN) AF: 0.512 AC: 5420 AN: 10582

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31209 AN: 67992

Other (OTH) AF: 0.502 AC: 1063 AN: 2116

Alfa AF: 0.475 Hom.: 72166

Bravo AF: 0.505

Asia WGS AF: 0.678 AC: 2355 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.15
PhyloP100		0.94
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: rs2059956; hg19: chr15-34123532;