Variant 2-46512074-A-G 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.638T>C(p.Met213Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ATP6V1E2
NM_001318063.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

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:

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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=0.023577005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1E2	NM_001318063.2 linkuse as main transcript	c.638T>C	p.Met213Thr	missense_variant	5/5	ENST00000522587.6	NP_001304992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ATP6V1E2	ENST00000522587.6 linkuse as main transcript	c.638T>C	p.Met213Thr	missense_variant	5/5	3	NM_001318063.2	ENSP00000428141	P1
ATP6V1E2	ENST00000306448.4 linkuse as main transcript	c.638T>C	p.Met213Thr	missense_variant	2/2	1		ENSP00000304891	P1
ATP6V1E2	ENST00000524249.5 linkuse as main transcript	n.776-21243T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249790

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134942

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Nov 19, 2022

The c.638T>C (p.M213T) alteration is located in exon 2 (coding exon 1) of the ATP6V1E2 gene. This alteration results from a T to C substitution at nucleotide position 638, causing the methionine (M) at amino acid position 213 to be replaced by a threonine (T). 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

0.085

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.054

DANN

Benign

0.61

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

2.7

N;N

REVEL

Benign

0.16

Sift

Benign

0.83

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;B

Vest4

0.053

MVP

0.12

MPC

0.015

ClinPred

0.029

GERP RS

-5.7

Varity_R

0.040

gMVP

0.32

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