rs7177922

Variant names:

• chr15-33616418-G-A
• rs7177922
• NM_001036.6:c.2357+3043G>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.2357+3043G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,082 control chromosomes in the GnomAD database, including 3,143 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 0.19 (3143 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.2357+3043G>A		intron_variant	Intron 19 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.2357+3043G>A		intron_variant	Intron 19 of 103	1	NM_001036.6	ENSP00000489262.1
RYR3	ENST00000389232.9	c.2357+3043G>A		intron_variant	Intron 19 of 103	5		ENSP00000373884.5
RYR3	ENST00000415757.7	c.2357+3043G>A		intron_variant	Intron 19 of 102	2		ENSP00000399610.3
RYR3	ENST00000634418.1	c.2357+3043G>A		intron_variant	Intron 19 of 101	5		ENSP00000489529.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29390 AN: 151964 Hom.: 3136 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.193 AC: 29427 AN: 152082 Hom.: 3143 Cov.: 33 AF XY: 0.198 AC XY: 14684 AN XY: 74316

African (AFR) AF: 0.115 AC: 4770 AN: 41500

American (AMR) AF: 0.261 AC: 3997 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3464

East Asian (EAS) AF: 0.161 AC: 829 AN: 5164

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2878 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14624 AN: 67978

Other (OTH) AF: 0.193 AC: 407 AN: 2106

Alfa AF: 0.209 Hom.: 6010

Bravo AF: 0.189

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.69
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: rs7177922; hg19: chr15-33908619;