rs200740143

chr15-33662351-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001036.6(RYR3):c.4821T>C(p.Tyr1607=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,820 control chromosomes in the GnomAD database, including 11 homozygotes. 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: 33)
  • Exomes 𝑓: 0.0028 (11 hom.)
• Consequence: RYR3 NM_001036.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.771

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 15-33662351-T-C is Benign according to our data. Variant chr15-33662351-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 461919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.771 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.4821T>C	p.Tyr1607=	synonymous_variant	35/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.4821T>C	p.Tyr1607=	synonymous_variant	35/104	1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.4821T>C	p.Tyr1607=	synonymous_variant	35/104	5		A1
RYR3	ENST00000415757.7	c.4821T>C	p.Tyr1607=	synonymous_variant	35/103	2		A2
RYR3	ENST00000634418.1	c.4821T>C	p.Tyr1607=	synonymous_variant	35/102	5

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 261 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00188 AC: 464 AN: 246396 Hom.: 1 AF XY: 0.00196 AC XY: 262 AN XY: 133692

Gnomad AFR exome AF: 0.000401

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.000903

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.000605

Gnomad NFE exome AF: 0.00321

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00280 AC: 4091 AN: 1460448 Hom.: 11 Cov.: 31 AF XY: 0.00274 AC XY: 1991 AN XY: 726362

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00164

Gnomad4 ASJ exome AF: 0.000959

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000932

Gnomad4 FIN exome AF: 0.000637

Gnomad4 NFE exome AF: 0.00342

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00171 AC: 261 AN: 152372 Hom.: 0 Cov.: 33 AF XY: 0.00149 AC XY: 111 AN XY: 74512

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00232 Hom.: 0

Bravo AF: 0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 02, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

RYR3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	1.9
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs200740143; hg19: chr15-33954552;