rs138546275

Variant names:

• chr1-16996255-C-A
• NM_022089.4:c.1352G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-16996255-C-A
• chr1-16996255-C-G
• chr1-16996255-C-T

Variant summary

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

The NM_022089.4(ATP13A2):​c.1352G>T​(p.Arg451Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R451Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP13A2 NM_022089.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002513
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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.1352G>T	p.Arg451Leu	missense_variant, splice_region_variant	Exon 14 of 29	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13	c.1352G>T	p.Arg451Leu	missense_variant, splice_region_variant	Exon 14 of 29	1	NM_022089.4	ENSP00000327214.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	7.5
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D;.;.;D;.;D
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.5	L;.;.;.;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.0	D;D;D;D;.;D
REVEL	Uncertain	0.40
Sift	Benign	0.15	T;T;T;T;.;D
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		0.087	B;.;.;.;.;.
Vest4		0.33
MutPred		0.69		Loss of solvent accessibility (P = 0.0079);.;.;.;.;.;
MVP		0.55
MPC		0.57
ClinPred		0.23	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.020
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: chr1-17322750;