rs56186751

Variant names:

• chr1-16993645-A-C
• rs56186751
• NM_022089.4:c.1733T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022089.4(ATP13A2):​c.1733T>G​(p.Val578Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP13A2 NM_022089.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.83

Genes affected

ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

ENSG00000226526 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4	c.1733T>G	p.Val578Gly	missense_variant	Exon 16 of 29	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13	c.1733T>G	p.Val578Gly	missense_variant	Exon 16 of 29	1	NM_022089.4	ENSP00000327214.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.30	B;.;.
Vest4		0.44
MutPred		0.64		Loss of stability (P = 0.0139);.;.;
MVP		0.91
MPC		0.98
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.86
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs56186751; hg19: chr1-17320140;