Variant 15-33861123-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001036.6(RYR3):c.14410A>G(p.Thr4804Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RYR3
NM_001036.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

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:

(HGNC:):

links:

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

AVEN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3830131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.14410A>G	p.Thr4804Ala	missense_variant	102/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.14410A>G	p.Thr4804Ala	missense_variant	102/104	1	NM_001036.6	P4	Q15413-1
	ENST00000560268.2 linkuse as main transcript	n.70-2029T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717112

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.14410A>G (p.T4804A) alteration is located in exon 102 (coding exon 102) of the RYR3 gene. This alteration results from a A to G substitution at nucleotide position 14410, causing the threonine (T) at amino acid position 4804 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.62

D;.;.;.;.;.

Eigen

Benign

0.067

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D;D;D;D;D

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.38

T;T;T;T;T;T

MetaSVM

Uncertain

0.65

MutationAssessor

Benign

1.0

L;.;.;.;.;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.8

.;D;D;.;.;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.010

.;D;T;.;.;.

Sift4G

Benign

0.15

.;.;.;.;.;T

Polyphen

0.17

B;B;.;.;.;.

Vest4

0.41

MutPred

0.26

Loss of glycosylation at T4804 (P = 0.0362);.;.;.;.;.;

MVP

0.80

MPC

0.74

ClinPred

0.97

GERP RS

5.2

Varity_R

0.27

gMVP

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over