Variant 15-33623951-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001036.6(RYR3):c.2502T>A(p.Ile834=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,613,934 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 592 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 530 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 15-33623951-T-A is Benign according to our data. Variant chr15-33623951-T-A is described in ClinVar as [Benign]. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.2502T>A	p.Ile834=	synonymous_variant	20/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.2502T>A	p.Ile834=	synonymous_variant	20/104	1	NM_001036.6	P4	Q15413-1
RYR3	ENST00000389232.9 linkuse as main transcript	c.2502T>A	p.Ile834=	synonymous_variant	20/104	5		A1
RYR3	ENST00000415757.7 linkuse as main transcript	c.2502T>A	p.Ile834=	synonymous_variant	20/103	2		A2	Q15413-2
RYR3	ENST00000634418.1 linkuse as main transcript	c.2502T>A	p.Ile834=	synonymous_variant	20/102	5

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

7332

AN:

152140

Hom.:

588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0142

AC:

3529

AN:

249072

Hom.:

232

AF XY:

0.0112

AC XY:

1516

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.00770

Gnomad ASJ exome

AF:

0.0417

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000984

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00575

AC:

8409

AN:

1461676

Hom.:

530

Cov.:

AF XY:

0.00508

AC XY:

3696

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.00899

Gnomad4 ASJ exome

AF:

0.0391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000451

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0483

AC:

7357

AN:

152258

Hom.:

592

Cov.:

AF XY:

0.0450

AC XY:

3347

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0550

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.99

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over