Variant 19-19646264-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020410.3(ATP13A1):c.3189T>G(p.Phe1063Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,944 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 14 hom., cov: 33)

Exomes 𝑓: 0.010 ( 90 hom. )

Consequence

ATP13A1
NM_020410.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.49

Variant links:

Genes affected

ATP13A1 (HGNC:24215): (ATPase 13A1) Enables transmembrane protein dislocase activity. Involved in extraction of mislocalized protein from ER membrane. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP13A1 links:

ATP13A1 (HGNC:):

ATP13A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075198114).

BP6

Variant 19-19646264-A-C is Benign according to our data. Variant chr19-19646264-A-C is described in ClinVar as [Benign]. Clinvar id is 781744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1080 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A1	NM_020410.3 linkuse as main transcript	c.3189T>G	p.Phe1063Leu	missense_variant	23/26	ENST00000357324.11	NP_065143.2	Q9HD20-1A0A024R7N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A1	ENST00000357324.11 linkuse as main transcript	c.3189T>G	p.Phe1063Leu	missense_variant	23/26	1	NM_020410.3	ENSP00000349877.6		Q9HD20-1

Frequencies

GnomAD3 genomes

AF:

0.00710

AC:

1080

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00709

AC:

1779

AN:

251046

Hom.:

AF XY:

0.00684

AC XY:

928

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.0104

AC:

15216

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

7370

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00270

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00850

GnomAD4 genome

AF:

0.00709

AC:

1080

AN:

152272

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

476

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00775

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0120

AC:

103

ExAC

AF:

0.00710

AC:

862

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.82

DANN

Benign

0.94

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-1.4

.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.46

N;N

REVEL

Benign

0.23

Sift

Benign

0.15

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

B;B

Vest4

0.24

MutPred

0.45

.;Loss of helix (P = 0.0626);

MVP

0.28

MPC

0.59

ClinPred

0.0079

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.024

gMVP

0.25

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