Variant 2-46512321-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001318063.2(ATP6V1E2):c.391G>A(p.Val131Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ATP6V1E2
NM_001318063.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.150

Variant links:

Genes affected

ATP6V1E2 (HGNC:18125): (ATPase H+ transporting V1 subunit E2) Predicted to enable P-type proton-exporting transporter activity. Predicted to act upstream of or within proton transmembrane transport. Predicted to be located in cytosol. Predicted to be part of proton-transporting two-sector ATPase complex, catalytic domain. [provided by Alliance of Genome Resources, Apr 2022]

ATP6V1E2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051760495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1E2	NM_001318063.2 link	c.391G>A	p.Val131Met	missense_variant	5/5	ENST00000522587.6	NP_001304992.1	Q96A05A0A140VKA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP6V1E2	ENST00000522587.6 link	c.391G>A	p.Val131Met	missense_variant	5/5	3	NM_001318063.2	ENSP00000428141.1	Q96A05
ATP6V1E2	ENST00000306448.4 link	c.391G>A	p.Val131Met	missense_variant	2/2	1		ENSP00000304891.4	Q96A05
ATP6V1E2	ENST00000524249.5 link	n.776-21490G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250206

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1460406

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2023

The c.391G>A (p.V131M) alteration is located in exon 2 (coding exon 1) of the ATP6V1E2 gene. This alteration results from a G to A substitution at nucleotide position 391, causing the valine (V) at amino acid position 131 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

0.52

N;N

REVEL

Benign

0.066

Sift

Benign

0.063

T;T

Sift4G

Benign

0.099

T;T

Polyphen

0.017

B;B

Vest4

0.090

MVP

0.14

MPC

0.016

ClinPred

0.024

GERP RS

1.6

Varity_R

0.092

gMVP

0.31

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