19-35554984-C-T

Position:

chr19-35554984-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000262623.4(ATP4A):c.2419G>A(p.Val807Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,613,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 1 hom. )

Consequence

ATP4A
ENST00000262623.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

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:

ATP4A (HGNC:):

ATP4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ATP4A. . Gene score misZ 2.8726 (greater than the threshold 3.09). Trascript score misZ 3.4596 (greater than threshold 3.09). GenCC has associacion of gene with familial gastric type 1 neuroendocrine tumor, gastric neuroendocrine neoplasm.

BP4

Computational evidence support a benign effect (MetaRNN=0.24252236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP4A	NM_000704.3 linkuse as main transcript	c.2419G>A	p.Val807Ile	missense_variant	16/22	ENST00000262623.4	NP_000695.2	P20648A0A384MR29Q658V6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP4A	ENST00000262623.4 linkuse as main transcript	c.2419G>A	p.Val807Ile	missense_variant	16/22	1	NM_000704.3	ENSP00000262623.2	P20648
ATP4A	ENST00000592131.5 linkuse as main transcript	n.792G>A		non_coding_transcript_exon_variant	4/10	2
ATP4A	ENST00000592767.2 linkuse as main transcript	n.*361G>A		non_coding_transcript_exon_variant	4/5	3		ENSP00000472323.2	M0R249
ATP4A	ENST00000592767.2 linkuse as main transcript	n.*361G>A		3_prime_UTR_variant	4/5	3		ENSP00000472323.2	M0R249

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251452

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.2419G>A (p.V807I) alteration is located in exon 16 (coding exon 16) of the ATP4A gene. This alteration results from a G to A substitution at nucleotide position 2419, causing the valine (V) at amino acid position 807 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.056

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.026

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.36

MutationTaster

Benign

0.76

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.17

REVEL

Benign

0.24

Sift

Benign

0.32

Sift4G

Benign

0.45

Polyphen

0.0020

Vest4

0.30

MVP

0.70

MPC

0.64

ClinPred

0.35

GERP RS

4.5

Varity_R

0.072

gMVP

0.61

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

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