rs12148702

Variant names:

• chr15-33636881-A-C
• rs12148702
• NM_001036.6:c.3556+331A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-33636881-A-C
• chr15-33636881-A-G
• chr15-33636881-A-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.3556+331A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,202 control chromosomes in the GnomAD database, including 51,673 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 0.82 (51673 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 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.3556+331A>C		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.3556+331A>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.3556+331A>C		intron	N/A	ENSP00000489262.1
	RYR3	ENST00000389232.9	TSL:5	c.3556+331A>C		intron	N/A	ENSP00000373884.5
	RYR3	ENST00000415757.7	TSL:2	c.3556+331A>C		intron	N/A	ENSP00000399610.3

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125034 AN: 152084 Hom.: 51618 Cov.: 33

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.822 AC: 125144 AN: 152202 Hom.: 51673 Cov.: 33 AF XY: 0.820 AC XY: 61000 AN XY: 74420

African (AFR) AF: 0.782 AC: 32435 AN: 41492

American (AMR) AF: 0.846 AC: 12952 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3098 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3500 AN: 5178

South Asian (SAS) AF: 0.711 AC: 3431 AN: 4828

European-Finnish (FIN) AF: 0.869 AC: 9202 AN: 10594

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57678 AN: 68010

Other (OTH) AF: 0.827 AC: 1750 AN: 2116

Alfa AF: 0.845 Hom.: 62197

Bravo AF: 0.821

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		0.29
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: rs12148702; hg19: chr15-33929082;