Variant chr3-194427078-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_001367549.1(ATP13A3):c.3122C>T(p.Ser1041Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000518 in 1,611,074 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 4 hom. )

Consequence

ATP13A3
NM_001367549.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

ATP13A3 (HGNC:24113): (ATPase 13A3) ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).[supplied by OMIM, Aug 2008]

ATP13A3 links:

ATP13A3 (HGNC:):

ATP13A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ATP13A3. . Gene score misZ 3.0145 (greater than the threshold 3.09). Trascript score misZ 3.7428 (greater than threshold 3.09). GenCC has associacion of gene with pulmonary arterial hypertension.

BP4

Computational evidence support a benign effect (MetaRNN=0.007133782).

BP6

Variant 3-194427078-G-A is Benign according to our data. Variant chr3-194427078-G-A is described in ClinVar as [Benign]. Clinvar id is 2057272.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000499 (76/152160) while in subpopulation SAS AF= 0.00104 (5/4816). AF 95% confidence interval is 0.000409. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A3	NM_001367549.1 linkuse as main transcript	c.3122C>T	p.Ser1041Leu	missense_variant	29/34	ENST00000645319.2	NP_001354478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A3	ENST00000645319.2 linkuse as main transcript	c.3122C>T	p.Ser1041Leu	missense_variant	29/34		NM_001367549.1	ENSP00000494937.2		A0A2R8Y635

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000976

AC:

241

AN:

246922

Hom.:

AF XY:

0.00105

AC XY:

141

AN XY:

133884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000311

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000520

AC:

758

AN:

1458914

Hom.:

Cov.:

AF XY:

0.000610

AC XY:

443

AN XY:

725648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.000499

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000990

Hom.:

Bravo

AF:

0.000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000277

AC:

ESP6500EA

AF:

0.000859

AC:

ExAC

AF:

0.000944

AC:

114

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ATP13A3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2019

This variant is classified as 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

Jan 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

T;T;.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.071

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;.;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.0071

T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.5

L;L;.;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;.;.;N;.

REVEL

Benign

0.18

Sift

Benign

0.41

T;.;.;T;.

Sift4G

Benign

0.14

T;.;.;T;.

Polyphen

0.0

B;B;.;B;.

Vest4

0.42

MVP

0.39

MPC

0.32

ClinPred

0.079

GERP RS

4.5

Varity_R

0.13

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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