Genetic Variant ATP4A:c.1500+5G>T (chr19-35558357-C-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000704.3(ATP4A):c.1500+5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,607,458 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 33 hom., cov: 32)

Exomes 𝑓: 0.020 ( 380 hom. )

Consequence

ATP4A
NM_000704.3 splice_region, intron

Scores

Splicing: ADA: 0.9997

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.65

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-35558357-C-A is Benign according to our data. Variant chr19-35558357-C-A is described in ClinVar as [Benign]. Clinvar id is 1600838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0159 (2416/152270) while in subpopulation NFE AF= 0.0222 (1509/68000). AF 95% confidence interval is 0.0213. There are 33 homozygotes in gnomad4. There are 1199 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP4A	NM_000704.3 link	c.1500+5G>T		splice_region_variant, intron_variant	Intron 10 of 21	ENST00000262623.4	NP_000695.2	P20648A0A384MR29Q658V6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP4A	ENST00000262623.4 link	c.1500+5G>T	splice_region_variant, intron_variant	Intron 10 of 21	1	NM_000704.3	ENSP00000262623.2	P20648
ENSG00000283907	ENST00000638356.1 link	n.72+330C>A	intron_variant	Intron 1 of 2	1
ENSG00000283907	ENST00000702449.1 link	n.100+330C>A	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2419

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00398

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0160

AC:

3793

AN:

236862

Hom.:

AF XY:

0.0160

AC XY:

2056

AN XY:

128318

show subpopulations

Gnomad AFR exome

AF:

0.00340

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.000512

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00579

Gnomad FIN exome

AF:

0.0291

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0201

AC:

29219

AN:

1455188

Hom.:

380

Cov.:

AF XY:

0.0197

AC XY:

14279

AN XY:

723202

show subpopulations

Gnomad4 AFR exome

AF:

0.00329

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.00104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00621

Gnomad4 FIN exome

AF:

0.0300

Gnomad4 NFE exome

AF:

0.0230

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0159

AC:

2416

AN:

152270

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1199

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00397

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.0274

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0178

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

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