Variant 19-19645978-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000357324.11(ATP13A1):c.3256C>G(p.Gln1086Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00456 in 1,611,606 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 27 hom. )

Consequence

ATP13A1
ENST00000357324.11 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-19645978-G-C is Benign according to our data. Variant chr19-19645978-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 769451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00465 (6784/1459274) while in subpopulation MID AF= 0.0251 (145/5768). AF 95% confidence interval is 0.0218. There are 27 homozygotes in gnomad4_exome. There are 3398 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 559 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A1	NM_020410.3 linkuse as main transcript	c.3256C>G	p.Gln1086Glu	missense_variant	24/26	ENST00000357324.11	NP_065143.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A1	ENST00000357324.11 linkuse as main transcript	c.3256C>G	p.Gln1086Glu	missense_variant	24/26	1	NM_020410.3	ENSP00000349877	P2	Q9HD20-1

Frequencies

GnomAD3 genomes

AF:

0.00366

AC:

557

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00456

AC:

1135

AN:

248864

Hom.:

AF XY:

0.00464

AC XY:

625

AN XY:

134638

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.000205

Gnomad NFE exome

AF:

0.00496

Gnomad OTH exome

AF:

0.00622

GnomAD4 exome

AF:

0.00465

AC:

6784

AN:

1459274

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

3398

AN XY:

725952

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.0345

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00301

Gnomad4 FIN exome

AF:

0.000255

Gnomad4 NFE exome

AF:

0.00443

Gnomad4 OTH exome

AF:

0.00631

GnomAD4 genome

AF:

0.00367

AC:

559

AN:

152332

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

264

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00469

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00663

Hom.:

Bravo

AF:

0.00378

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00422

AC:

513

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00658

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 29, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	ATP13A1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

.;N

MutationTaster

Benign

0.84

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

0.41

N;N

REVEL

Benign

0.076

Sift

Benign

0.87

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.27

MVP

0.41

MPC

0.55

ClinPred

0.0059

GERP RS

2.6

Varity_R

0.059

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 3

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