Variant rs41279202 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001036.6(RYR3):c.855A>T(p.Arg285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,613,722 control chromosomes in the GnomAD database, including 1,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 99 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1323 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.28

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=-0.56).

BP6

Variant 15-33550199-A-T is Benign according to our data. Variant chr15-33550199-A-T is described in ClinVar as [Benign]. Clinvar id is 461971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0304 (4633/152268) while in subpopulation NFE AF= 0.045 (3064/68018). AF 95% confidence interval is 0.0437. There are 99 homozygotes in gnomad4. There are 2165 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 99 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.855A>T	p.Arg285=	synonymous_variant	10/104	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.855A>T	p.Arg285=	synonymous_variant	10/104	1	NM_001036.6	ENSP00000489262	P4	Q15413-1
RYR3	ENST00000389232.9 linkuse as main transcript	c.855A>T	p.Arg285=	synonymous_variant	10/104	5		ENSP00000373884	A1
RYR3	ENST00000415757.7 linkuse as main transcript	c.855A>T	p.Arg285=	synonymous_variant	10/103	2		ENSP00000399610	A2	Q15413-2
RYR3	ENST00000634418.1 linkuse as main transcript	c.855A>T	p.Arg285=	synonymous_variant	10/102	5		ENSP00000489529

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4634

AN:

152150

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0312

AC:

7759

AN:

248576

Hom.:

145

AF XY:

0.0319

AC XY:

4304

AN XY:

134770

show subpopulations

Gnomad AFR exome

AF:

0.00734

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0789

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0428

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0402

AC:

58786

AN:

1461454

Hom.:

1323

Cov.:

AF XY:

0.0399

AC XY:

29015

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00732

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0797

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0449

Gnomad4 OTH exome

AF:

0.0367

GnomAD4 genome

AF:

0.0304

AC:

4633

AN:

152268

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

2165

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00847

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0847

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.0450

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0447

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0468

EpiControl

AF:

0.0423

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 29, 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

-0.56

CADD

Benign

3.8

DANN

Benign

0.60

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