NM_000704.3:c.2832T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000704.3(ATP4A):​c.2832T>A​(p.Asp944Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ATP4A
NM_000704.3 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP4ANM_000704.3 linkc.2832T>A p.Asp944Glu missense_variant Exon 19 of 22 ENST00000262623.4 NP_000695.2 P20648A0A384MR29Q658V6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP4AENST00000262623.4 linkc.2832T>A p.Asp944Glu missense_variant Exon 19 of 22 1 NM_000704.3 ENSP00000262623.2 P20648
ATP4AENST00000592131.5 linkn.1225T>A non_coding_transcript_exon_variant Exon 7 of 10 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2832T>A (p.D944E) alteration is located in exon 19 (coding exon 19) of the ATP4A gene. This alteration results from a T to A substitution at nucleotide position 2832, causing the aspartic acid (D) at amino acid position 944 to be replaced by a glutamic acid (E). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
7.5
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.69
D
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.42
N
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.60
D
MetaRNN
Pathogenic
0.90
D
MetaSVM
Pathogenic
0.85
D
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.9
D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.78
P
Vest4
0.84
MutPred
0.63
Loss of MoRF binding (P = 0.0837);
MVP
0.90
MPC
1.6
ClinPred
0.99
D
GERP RS
-5.5
Varity_R
0.55
gMVP
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36042402; API