Genetic Variant NM_000704.3:c.1501-42C>T (chr19-35557889-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000704.3(ATP4A):c.1501-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,060,460 control chromosomes in the GnomAD database, including 57,848 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6608 hom., cov: 23)

Exomes 𝑓: 0.28 ( 51240 hom. )

Consequence

ATP4A
NM_000704.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.363

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP4A	NM_000704.3 link	c.1501-42C>T		intron_variant	Intron 10 of 21	ENST00000262623.4	NP_000695.2	P20648A0A384MR29Q658V6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP4A	ENST00000262623.4 link	c.1501-42C>T		intron_variant	Intron 10 of 21	1	NM_000704.3	ENSP00000262623.2		P20648

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

41499

AN:

146524

Hom.:

6610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.406

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.233

AC:

8600

AN:

36950

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.0948

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.278

AC:

254266

AN:

913830

Hom.:

51240

Cov.:

AF XY:

0.284

AC XY:

127610

AN XY:

449648

show subpopulations

African (AFR)

AF:

0.110

AC:

2560

AN:

23326

American (AMR)

AF:

0.160

AC:

2879

AN:

17998

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

5065

AN:

15420

East Asian (EAS)

AF:

0.166

AC:

4986

AN:

30122

South Asian (SAS)

AF:

0.328

AC:

16265

AN:

49574

European-Finnish (FIN)

AF:

0.364

AC:

10743

AN:

29510

Middle Eastern (MID)

AF:

0.361

AC:

970

AN:

2684

European-Non Finnish (NFE)

AF:

0.283

AC:

199446

AN:

704940

Other (OTH)

AF:

0.282

AC:

11352

AN:

40256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.559

Heterozygous variant carriers

6846

13693

20539

27386

34232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5170

10340

15510

20680

25850

<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:

0.283

AC:

41498

AN:

146630

Hom.:

6608

Cov.:

AF XY:

0.281

AC XY:

20042

AN XY:

71346

show subpopulations

African (AFR)

AF:

0.151

AC:

5971

AN:

39658

American (AMR)

AF:

0.233

AC:

3451

AN:

14832

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1247

AN:

3410

East Asian (EAS)

AF:

0.236

AC:

1157

AN:

4906

South Asian (SAS)

AF:

0.336

AC:

1503

AN:

4468

European-Finnish (FIN)

AF:

0.347

AC:

3435

AN:

9896

Middle Eastern (MID)

AF:

0.399

AC:

114

AN:

286

European-Non Finnish (NFE)

AF:

0.357

AC:

23640

AN:

66278

Other (OTH)

AF:

0.312

AC:

632

AN:

2024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1339

2678

4017

5356

6695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.301

Hom.:

769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.7

(source)

DANN

Benign

0.94

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over