Variant 17-3930371-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005173.4(ATP2A3):c.2674G>A(p.Glu892Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00415 in 1,613,738 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 26 hom. )

Consequence

ATP2A3
NM_005173.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.17

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021290064).

BP6

Variant 17-3930371-C-T is Benign according to our data. Variant chr17-3930371-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041510.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2A3	NM_005173.4 linkuse as main transcript	c.2674G>A	p.Glu892Lys	missense_variant	18/21	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.2674G>A	p.Glu892Lys	missense_variant	18/21	1	NM_005173.4	ENSP00000380234.3		Q93084-2

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

457

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00486

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00328

AC:

818

AN:

249296

Hom.:

AF XY:

0.00333

AC XY:

450

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.00100

Gnomad AMR exome

AF:

0.00395

Gnomad ASJ exome

AF:

0.00220

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000394

Gnomad FIN exome

AF:

0.00177

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00395

GnomAD4 exome

AF:

0.00427

AC:

6235

AN:

1461370

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

3040

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00379

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000395

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.00503

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152368

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00487

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00431

Hom.:

Bravo

AF:

0.00312

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00327

AC:

396

EpiCase

AF:

0.00480

EpiControl

AF:

0.00505

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATP2A3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2022

This variant is classified as likely 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

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

.;.;.;.;.;D;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.032

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D;.;D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.016

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.013

MutationAssessor

Benign

1.9

M;M;M;.;M;M;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

N;N;N;.;N;N;N;.

REVEL

Uncertain

0.61

Sift

Benign

0.20

T;T;T;.;T;T;T;.

Sift4G

Benign

0.42

T;T;T;D;T;T;T;D

Polyphen

0.0060

B;B;B;.;.;B;P;.

Vest4

0.71

MVP

0.69

MPC

0.77

ClinPred

0.038

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.93

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