rs573196719

Variant names:

• chr1-16986172-T-A
• rs573196719
• ENST00000341676.9:c.3290A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-16986172-T-A
• chr1-16986172-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001141974.3(ATP13A2):​c.3290A>T​(p.His1097Leu) 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 benign outcome for this variant. 15/18 in silico tools predict a benign 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. H1097R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP13A2 NM_001141974.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62
• Publications: 0 publications found

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]

ATP13A2 Gene-Disease associations (from GenCC):

• Kufor-Rakeb syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Illumina, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive spastic paraplegia type 78

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• parkinsonism due to ATP13A2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000226526 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061460793).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141974.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	NM_022089.4	MANE Select	c.*49A>T		3_prime_UTR	Exon 29 of 29	NP_071372.1	Q9NQ11-1
	ATP13A2	NM_001141974.3		c.3290A>T	p.His1097Leu	missense	Exon 27 of 27	NP_001135446.1	Q9NQ11-2
	ATP13A2	NM_001141973.3		c.*49A>T		3_prime_UTR	Exon 29 of 29	NP_001135445.1	Q9NQ11-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	ENST00000341676.9	TSL:1	c.3290A>T	p.His1097Leu	missense	Exon 27 of 27	ENSP00000341115.5	Q9NQ11-2
	ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.*49A>T		3_prime_UTR	Exon 29 of 29	ENSP00000327214.8	Q9NQ11-1
	ATP13A2	ENST00000452699.5	TSL:1	c.*49A>T		3_prime_UTR	Exon 29 of 29	ENSP00000413307.1	Q9NQ11-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	2.6
DANN	Benign	0.85
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.29	T
PhyloP100		-3.6
PROVEAN	Benign	0.10	N
REVEL	Benign	0.24
Sift	Uncertain	0.015	D
Sift4G	Benign	0.35	T
Vest4		0.27
MutPred		0.15		Gain of sheet (P = 0.0266)
MVP		0.21
ClinPred		0.086	T
GERP RS		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs573196719; hg19: chr1-17312667;