rs78959515

Variant names:

• chr15-33563714-T-C
• rs78959515
• NM_001036.6:c.1146+704T>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.1146+704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 152,254 control chromosomes in the GnomAD database, including 487 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 0.071 (487 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.1146+704T>C		intron_variant	Intron 11 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.1146+704T>C		intron_variant	Intron 11 of 103	1	NM_001036.6	ENSP00000489262.1
RYR3	ENST00000389232.9	c.1146+704T>C		intron_variant	Intron 11 of 103	5		ENSP00000373884.5
RYR3	ENST00000415757.7	c.1146+704T>C		intron_variant	Intron 11 of 102	2		ENSP00000399610.3
RYR3	ENST00000634418.1	c.1146+704T>C		intron_variant	Intron 11 of 101	5		ENSP00000489529.1

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10804 AN: 152136 Hom.: 487 Cov.: 33

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0689

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0654

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

GnomAD4 genome AF: 0.0710 AC: 10812 AN: 152254 Hom.: 487 Cov.: 33 AF XY: 0.0724 AC XY: 5386 AN XY: 74440

African (AFR) AF: 0.0490 AC: 2037 AN: 41542

American (AMR) AF: 0.0535 AC: 819 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0685 AC: 331 AN: 4832

European-Finnish (FIN) AF: 0.118 AC: 1246 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5771 AN: 68008

Other (OTH) AF: 0.0643 AC: 136 AN: 2116

Alfa AF: 0.0795 Hom.: 172

Bravo AF: 0.0653

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.26
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: rs78959515; hg19: chr15-33855915;