Variant rs55650127 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001036.6(RYR3):c.9759C>T(p.Asp3253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,613,850 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 19 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.07

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 15-33788387-C-T is Benign according to our data. Variant chr15-33788387-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0038 (5560/1461602) while in subpopulation MID AF= 0.0281 (162/5768). AF 95% confidence interval is 0.0246. There are 19 homozygotes in gnomad4_exome. There are 2782 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.9759C>T	p.Asp3253=	synonymous_variant	67/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.9759C>T	p.Asp3253=	synonymous_variant	67/104	1	NM_001036.6	P4	Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

809

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00412

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00418

AC:

1042

AN:

249120

Hom.:

AF XY:

0.00414

AC XY:

560

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.00962

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.000464

Gnomad NFE exome

AF:

0.00484

Gnomad OTH exome

AF:

0.00728

GnomAD4 exome

AF:

0.00380

AC:

5560

AN:

1461602

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

2782

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00274

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00461

GnomAD4 genome

AF:

0.00532

AC:

810

AN:

152248

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00944

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00412

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.00568

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00652

ClinVar

Significance: Benign/Likely 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

Invitae

Jan 18, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

RYR3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.095

DANN

Benign

0.52

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