NM_001036.6:c.1573+431T>C

Variant names:

• chr15-33582074-T-C
• rs877087
• NM_001036.6:c.1573+431T>C

Variant summary

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

The NM_001036.6(RYR3):​c.1573+431T>C 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 152,106 control chromosomes in the GnomAD database, including 20,793 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 (20793 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 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.1573+431T>C		intron	N/A	NP_001027.3
	RYR3	NM_001243996.4		c.1573+431T>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.1573+431T>C		intron	N/A	ENSP00000489262.1	Q15413-1
	RYR3	ENST00000389232.9	TSL:5	c.1573+431T>C		intron	N/A	ENSP00000373884.5	A0A0X1KG73
	RYR3	ENST00000415757.7	TSL:2	c.1573+431T>C		intron	N/A	ENSP00000399610.3	Q15413-2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77501 AN: 151988 Hom.: 20780 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.510 AC: 77536 AN: 152106 Hom.: 20793 Cov.: 33 AF XY: 0.499 AC XY: 37133 AN XY: 74364

African (AFR) AF: 0.573 AC: 23775 AN: 41466

American (AMR) AF: 0.419 AC: 6403 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3466

East Asian (EAS) AF: 0.0484 AC: 251 AN: 5190

South Asian (SAS) AF: 0.298 AC: 1440 AN: 4828

European-Finnish (FIN) AF: 0.464 AC: 4907 AN: 10568

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36673 AN: 67982

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.527 Hom.: 37428

Bravo AF: 0.511

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.66
PhyloP100		-1.7
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: rs877087; hg19: chr15-33874275;