dbSNP rs139397080: ATP4A:p.Ser530Asn (chr19-35557759-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000704.3(ATP4A):c.1589G>A(p.Ser530Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0033 in 1,593,374 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

ATP4A
NM_000704.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.90

Publications

3 publications found

Variant links:

Genes affected

ATP4A (HGNC:819): (ATPase H+/K+ transporting subunit alpha) The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes a catalytic alpha subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

ATP4A links:

LINC01766 (HGNC:52556): (long intergenic non-protein coding RNA 1766)

LINC01766 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013930798).

BP6

Variant 19-35557759-C-T is Benign according to our data. Variant chr19-35557759-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 717755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000704.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP4A	NM_000704.3	MANE Select	c.1589G>A	p.Ser530Asn	missense	Exon 11 of 22	NP_000695.2	P20648

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP4A	ENST00000262623.4	TSL:1 MANE Select	c.1589G>A	p.Ser530Asn	missense	Exon 11 of 22	ENSP00000262623.2	P20648
ATP4A	ENST00000592131.5	TSL:2	n.49G>A		non_coding_transcript_exon	Exon 1 of 10
LINC01766	ENST00000716278.1		n.82C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00219

AC:

503

AN:

229704

AF XY:

0.00235

show subpopulations

Gnomad AFR exome

AF:

0.000354

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.000214

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000343

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00343

AC:

4936

AN:

1441068

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2384

AN XY:

713380

show subpopulations

African (AFR)

AF:

0.000395

AC:

AN:

32936

American (AMR)

AF:

0.00104

AC:

AN:

43374

Ashkenazi Jewish (ASJ)

AF:

0.000272

AC:

AN:

25700

East Asian (EAS)

AF:

0.00

AC:

AN:

38952

South Asian (SAS)

AF:

0.00142

AC:

121

AN:

85196

European-Finnish (FIN)

AF:

0.000593

AC:

AN:

52302

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

5052

European-Non Finnish (NFE)

AF:

0.00413

AC:

4537

AN:

1098328

Other (OTH)

AF:

0.00294

AC:

174

AN:

59228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

170

340

510

680

850

<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:

0.00207

AC:

316

AN:

152306

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41574

American (AMR)

AF:

0.000719

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00397

AC:

270

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00309

Hom.:

Bravo

AF:

0.00211

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00362

AC:

ExAC

AF:

0.00230

AC:

278

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.065

MetaRNN

Benign

0.014

MetaSVM

Uncertain

-0.048

MutationAssessor

Benign

1.6

PhyloP100

3.9

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.45

Sift

Uncertain

0.013

Sift4G

Benign

0.12

Polyphen

0.39

Vest4

0.53

MVP

0.80

MPC

0.81

ClinPred

0.045

GERP RS

3.8

Varity_R

0.23

gMVP

0.71

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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