Variant rs758641 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005173.4(ATP2A3):c.1302T>C(p.Tyr434Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,542 control chromosomes in the GnomAD database, including 149,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.41 ( 13315 hom., cov: 31)

Exomes 𝑓: 0.42 ( 136068 hom. )

Consequence

ATP2A3
NM_005173.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.116

Variant links:

Genes affected

ATP2A3 (HGNC:813): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ATP2A3 links:

ATP2A3 (HGNC:):

ATP2A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-3943508-A-G is Benign according to our data. Variant chr17-3943508-A-G is described in ClinVar as [Benign]. Clinvar id is 3059760.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.116 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2A3	NM_005173.4 linkuse as main transcript	c.1302T>C	p.Tyr434Tyr	synonymous_variant	11/21	ENST00000397041.8	NP_005164.2	Q93084-2A8K9K1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8 linkuse as main transcript	c.1302T>C	p.Tyr434Tyr	synonymous_variant	11/21	1	NM_005173.4	ENSP00000380234.3		Q93084-2

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62078

AN:

151730

Hom.:

13298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.0832

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.548

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.397

AC:

99922

AN:

251406

Hom.:

21404

AF XY:

0.398

AC XY:

54149

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.578

Gnomad EAS exome

AF:

0.0793

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

AF:

0.425

AC:

620526

AN:

1461694

Hom.:

136068

Cov.:

AF XY:

0.423

AC XY:

307315

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.376

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.0710

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.334

Gnomad4 NFE exome

AF:

0.447

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.409

AC:

62140

AN:

151848

Hom.:

13315

Cov.:

AF XY:

0.404

AC XY:

29950

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.381

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.590

Gnomad4 EAS

AF:

0.0827

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.433

Alfa

AF:

0.444

Hom.:

14101

Bravo

AF:

0.417

Asia WGS

AF:

0.207

AC:

722

AN:

3478

EpiCase

AF:

0.464

EpiControl

AF:

0.462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATP2A3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.0

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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