rs9014

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005765.3(ATP6AP2):c.268C>G(p.Pro90Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,209,214 control chromosomes in the GnomAD database, including 2,031 homozygotes. There are 24,408 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 106 hom., 1385 hem., cov: 23)

Exomes 𝑓: 0.065 ( 1925 hom. 23023 hem. )

Consequence

ATP6AP2
NM_005765.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.393

Variant links:

Genes affected

ATP6AP2 (HGNC:18305): (ATPase H+ transporting accessory protein 2) This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]

ATP6AP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012736917).

BP6

Variant X-40591333-C-G is Benign according to our data. Variant chrX-40591333-C-G is described in ClinVar as [Benign]. Clinvar id is 95311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40591333-C-G is described in Lovd as [Likely_benign]. Variant chrX-40591333-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3 linkuse as main transcript	c.268C>G	p.Pro90Ala	missense_variant	3/9	ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2 linkuse as main transcript	c.268C>G	p.Pro90Ala	missense_variant	3/9	1	NM_005765.3	P3	O75787-1

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

5130

AN:

111833

Hom.:

107

Cov.:

AF XY:

0.0407

AC XY:

1386

AN XY:

34047

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.0557

Gnomad AMR

AF:

0.0561

Gnomad ASJ

AF:

0.0699

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.0424

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0698

GnomAD3 exomes

AF:

0.0436

AC:

7988

AN:

183309

Hom.:

182

AF XY:

0.0434

AC XY:

2940

AN XY:

67745

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0681

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0678

Gnomad OTH exome

AF:

0.0583

GnomAD4 exome

AF:

0.0655

AC:

71851

AN:

1097325

Hom.:

1925

Cov.:

AF XY:

0.0634

AC XY:

23023

AN XY:

362895

show subpopulations

Gnomad4 AFR exome

AF:

0.00967

Gnomad4 AMR exome

AF:

0.0398

Gnomad4 ASJ exome

AF:

0.0700

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.0168

Gnomad4 NFE exome

AF:

0.0768

Gnomad4 OTH exome

AF:

0.0587

GnomAD4 genome

AF:

0.0458

AC:

5125

AN:

111889

Hom.:

106

Cov.:

AF XY:

0.0406

AC XY:

1385

AN XY:

34113

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.0559

Gnomad4 ASJ

AF:

0.0699

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0706

Gnomad4 OTH

AF:

0.0689

Alfa

AF:

0.0558

Hom.:

1220

Bravo

AF:

0.0491

TwinsUK

AF:

0.0874

AC:

324

ALSPAC

AF:

0.0810

AC:

234

ESP6500AA

AF:

0.0112

AC:

ESP6500EA

AF:

0.0719

AC:

484

ExAC

AF:

0.0422

AC:

5124

EpiCase

AF:

0.0731

EpiControl

AF:

0.0744

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2013	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Syndromic X-linked intellectual disability Hedera type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2015

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

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

DANN

Benign

0.88

DEOGEN2

Benign

0.026

T;T;.;T;T;T;.;T;.;T;T;T;.;T;T

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

.;N;N;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.59

.;.;.;.;.;.;N;.;.;.;.;.;.;.;.

REVEL

Benign

0.11

Sift

Benign

0.78

.;.;.;.;.;.;T;.;.;.;.;.;.;.;.

Sift4G

Benign

0.47

.;.;.;.;.;.;T;.;.;.;.;.;.;.;.

Polyphen

0.0

.;B;.;.;.;.;.;.;.;.;.;B;.;.;.

Vest4

0.047

MPC

0.51

ClinPred

0.0019

GERP RS

-0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.46

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