Variant 3-193402746-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032279.4(ATP13A4):c.3497C>T(p.Pro1166Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000703 in 1,608,448 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 10 hom. )

Consequence

ATP13A4
NM_032279.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.67

Variant links:

Genes affected

ATP13A4 (HGNC:25422): (ATPase 13A4) Predicted to enable ATPase-coupled cation transmembrane transporter activity. Predicted to be involved in cellular calcium ion homeostasis. Predicted to be located in endoplasmic reticulum membrane and endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP13A4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006216049).

BP6

Variant 3-193402746-G-A is Benign according to our data. Variant chr3-193402746-G-A is described in ClinVar as [Benign]. Clinvar id is 734313.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A4	NM_032279.4 link	c.3497C>T	p.Pro1166Leu	missense_variant	30/30	ENST00000342695.9	NP_115655.2	Q4VNC1-1B3KU47
ATP13A4	XM_047449063.1 link	c.3626C>T	p.Pro1209Leu	missense_variant	32/32		XP_047305019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A4	ENST00000342695.9 link	c.3497C>T	p.Pro1166Leu	missense_variant	30/30	1	NM_032279.4	ENSP00000339182.4		Q4VNC1-1

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00116

AC:

292

AN:

251368

Hom.:

AF XY:

0.00147

AC XY:

200

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00666

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000716

AC:

1043

AN:

1456226

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

685

AN XY:

724882

show subpopulations

Gnomad4 AFR exome

AF:

0.000360

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00502

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00783

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000578

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000455

Hom.:

Bravo

AF:

0.000370

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00134

AC:

163

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ATP13A4-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

.;.;M

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-8.5

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.048

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.16

.;.;B

Vest4

0.32

MVP

0.54

MPC

0.14

ClinPred

0.094

GERP RS

4.1

Varity_R

0.22

gMVP

0.69

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

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