GeneBe

rs573530240

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198505.4(ATP13A5):​c.2687G>C​(p.Arg896Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R896Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ATP13A5
NM_198505.4 missense

Scores

11
4
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.99

Publications

0 publications found
Variant links:
Genes affected
ATP13A5 (HGNC:31789): (ATPase 13A5) This gene encodes a member of the P5 subfamily of P-type transport ATPases. P-type ATPases form a large superfamily of cation and lipid pumps that transport inorganic cations and other substrates across cell membranes. P5 ATPases are localized to membranes of the endoplasmic reticulum (ER) and serve many important functions including transport of cargo proteins to the Golgi, glycosylation and cell wall biosynthesis, control of protein insertion orientation, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) degradation, and sensitivity to unfolded protein response (UPR) activators. The encoded protein is organized into three cytoplasmic domains (A, P, and N) and two membrane-embedded domains (T and S). The N-domain binds ATP and serves as a built-in protein kinase, which phosphorylates the P-domain. The A-domain is an intrinsic protein phosphatase, which dephosphorylates the P-domain once during each catalytic cycle. [provided by RefSeq, Jul 2017]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.977

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198505.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATP13A5
NM_198505.4
MANE Select
c.2687G>Cp.Arg896Pro
missense
Exon 24 of 30NP_940907.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATP13A5
ENST00000342358.9
TSL:1 MANE Select
c.2687G>Cp.Arg896Pro
missense
Exon 24 of 30ENSP00000341942.4Q4VNC0
ATP13A5
ENST00000495496.1
TSL:5
n.509G>C
non_coding_transcript_exon
Exon 6 of 12

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.53
D
BayesDel_noAF
Pathogenic
0.53
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.077
D
MetaRNN
Pathogenic
0.98
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.1
H
PhyloP100
6.0
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-6.3
D
REVEL
Pathogenic
0.92
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.99
MutPred
0.88
Loss of methylation at R896 (P = 0.0339)
MVP
0.79
MPC
0.50
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.85
gMVP
0.94
Mutation Taster
=86/14
polymorphism

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

Other links and lift over

dbSNP: rs573530240; hg19: chr3-193019088; API