chr1-16987159-C-T

Position:

chr1-16987159-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022089.4(ATP13A2):c.2970G>A(p.Val990=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,612,896 control chromosomes in the GnomAD database, including 203,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14650 hom., cov: 33)

Exomes 𝑓: 0.50 ( 188913 hom. )

Consequence

ATP13A2
NM_022089.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -0.854

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-16987159-C-T is Benign according to our data. Variant chr1-16987159-C-T is described in ClinVar as [Benign]. Clinvar id is 128470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16987159-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.854 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A2	NM_022089.4 linkuse as main transcript	c.2970G>A	p.Val990=	synonymous_variant	26/29	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 linkuse as main transcript	c.2970G>A	p.Val990=	synonymous_variant	26/29	1	NM_022089.4	ENSP00000327214	A1	Q9NQ11-1
	ENST00000446261.1 linkuse as main transcript	n.187+8047C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63475

AN:

151926

Hom.:

14645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.465

AC:

115513

AN:

248224

Hom.:

27876

AF XY:

0.471

AC XY:

63408

AN XY:

134658

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

AF:

0.504

AC:

735772

AN:

1460852

Hom.:

188913

Cov.:

AF XY:

0.504

AC XY:

365963

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.475

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.418

AC:

63492

AN:

152044

Hom.:

14650

Cov.:

AF XY:

0.413

AC XY:

30710

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.447

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.274

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.527

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.497

Hom.:

10301

Bravo

AF:

0.407

Asia WGS

AF:

0.339

AC:

1178

AN:

3478

EpiCase

AF:

0.516

EpiControl

AF:

0.518

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 71% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 66. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 19, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kufor-Rakeb syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive spastic paraplegia type 78

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.12

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over