NM_000704.3:c.2832T>A

Variant names:

• chr19-35551500-A-T
• NM_000704.3:c.2832T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

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]

ACMG classification

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
ATP4A	NM_000704.3	c.2832T>A	p.Asp944Glu	missense_variant	Exon 19 of 22	ENST00000262623.4	NP_000695.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP4A	ENST00000262623.4	c.2832T>A	p.Asp944Glu	missense_variant	Exon 19 of 22	1	NM_000704.3	ENSP00000262623.2
ATP4A	ENST00000592131.5	n.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

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;