17-3930371-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E892G) has been classified as Uncertain significance.

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

Publications

8 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3041510.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2A3	NM_005173.4	MANE Select	c.2674G>A	p.Glu892Lys	missense	Exon 18 of 21	NP_005164.2
ATP2A3	NM_174953.3		c.2674G>A	p.Glu892Lys	missense	Exon 18 of 23	NP_777613.1	Q93084-5
ATP2A3	NM_174954.3		c.2674G>A	p.Glu892Lys	missense	Exon 18 of 23	NP_777614.1	Q93084-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2A3	ENST00000397041.8	TSL:1 MANE Select	c.2674G>A	p.Glu892Lys	missense	Exon 18 of 21	ENSP00000380234.3	Q93084-2
ATP2A3	ENST00000397043.7	TSL:1	c.2674G>A	p.Glu892Lys	missense	Exon 18 of 21	ENSP00000380236.3	Q93084-4
ATP2A3	ENST00000570845.5	TSL:1	c.1G>A	p.Glu1Lys	missense	Exon 1 of 6	ENSP00000461480.1	A0A0C4DGN3

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

GnomAD2 exomes

AF:

0.00328

AC:

818

AN:

249296

AF XY:

0.00333

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 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

African (AFR)

AF:

0.000687

AC:

AN:

33470

American (AMR)

AF:

0.00379

AC:

169

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.000395

AC:

AN:

86156

European-Finnish (FIN)

AF:

0.00240

AC:

128

AN:

53292

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00503

AC:

5591

AN:

1111844

Other (OTH)

AF:

0.00366

AC:

221

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

421

843

1264

1686

2107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152368

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000769

AC:

AN:

41588

American (AMR)

AF:

0.00327

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00487

AC:

331

AN:

68036

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00404

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ATP2A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.032

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.016

MetaSVM

Uncertain

-0.013

MutationAssessor

Benign

1.9

PhyloP100

6.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.61

Sift

Benign

0.20

Sift4G

Benign

0.42

Polyphen

0.0060

Vest4

0.71

MVP

0.69

MPC

0.77

ClinPred

0.038

GERP RS

3.8

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.35

gMVP

0.93

Mutation Taster

=25/75

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over