NM_001036.6:c.1788+10G>C

Variant names:

• chr15-33586126-G-C
• rs146892882
• NM_001036.6:c.1788+10G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001036.6(RYR3):​c.1788+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,516,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.342
• Publications: 0 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=-0.82).
• BP6: Variant 15-33586126-G-C is Benign according to our data. Variant chr15-33586126-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 461885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1788+10G>C		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.1788+10G>C		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.1788+10G>C		intron	N/A	ENSP00000489262.1	Q15413-1
	RYR3	ENST00000389232.9	TSL:5	c.1788+10G>C		intron	N/A	ENSP00000373884.5	A0A0X1KG73
	RYR3	ENST00000415757.7	TSL:2	c.1788+10G>C		intron	N/A	ENSP00000399610.3	Q15413-2

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 264 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000450 AC: 112 AN: 248698 AF XY: 0.000385

Gnomad AFR exome AF: 0.00628

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000183 AC: 249 AN: 1364090 Hom.: 0 Cov.: 21 AF XY: 0.000159 AC XY: 109 AN XY: 684396

African (AFR) AF: 0.00621 AC: 196 AN: 31562

American (AMR) AF: 0.000337 AC: 15 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 39208

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000360 AC: 2 AN: 5548

European-Non Finnish (NFE) AF: 0.00000978 AC: 10 AN: 1022746

Other (OTH) AF: 0.000438 AC: 25 AN: 57136

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.00175 AC XY: 130 AN XY: 74492

African (AFR) AF: 0.00623 AC: 259 AN: 41576

American (AMR) AF: 0.000261 AC: 4 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000854 Hom.: 0

Bravo AF: 0.00189

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Epileptic encephalopathy (1)
-	-	1	not provided (1)
-	-	1	RYR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		0.34

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: rs146892882; hg19: chr15-33878327;