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

Variant summary

Our verdict is Benign. Variant got -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

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:

ENSG00000283907 (HGNC:):

ENSG00000283907 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 717755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP4A	NM_000704.3 link	c.1589G>A	p.Ser530Asn	missense_variant	Exon 11 of 22	ENST00000262623.4	NP_000695.2	P20648A0A384MR29Q658V6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP4A	ENST00000262623.4 link	c.1589G>A	p.Ser530Asn	missense_variant	Exon 11 of 22	1	NM_000704.3	ENSP00000262623.2		P20648

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

GnomAD3 exomes

AF:

0.00219

AC:

503

AN:

229704

Hom.:

AF XY:

0.00235

AC XY:

297

AN XY:

126320

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 SAS exome

AF:

0.00146

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

Gnomad4 AFR exome

AF:

0.000395

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.000272

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00142

Gnomad4 FIN exome

AF:

0.000593

Gnomad4 NFE exome

AF:

0.00413

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.00207

AC:

316

AN:

152306

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00303

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

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

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

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

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

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