chr7-149874130-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145230.4(ATP6V0E2):c.65T>C(p.Ile22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,549,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I22V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 1 hom. )

Consequence

ATP6V0E2
NM_145230.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Publications

0 publications found

Variant links:

Genes affected

ATP6V0E2 (HGNC:21723): (ATPase H+ transporting V0 subunit e2) Multisubunit vacuolar-type proton pumps, or H(+)-ATPases, acidify various intracellular compartments, such as vacuoles, clathrin-coated and synaptic vesicles, endosomes, lysosomes, and chromaffin granules. H(+)-ATPases are also found in plasma membranes of specialized cells, where they play roles in urinary acidification, bone resorption, and sperm maturation. Multiple subunits form H(+)-ATPases, with proteins of the V1 class hydrolyzing ATP for energy to transport H+, and proteins of the V0 class forming an integral membrane domain through which H+ is transported. ATP6V0E2 encodes an isoform of the H(+)-ATPase V0 e subunit, an essential proton pump component (Blake-Palmer et al., 2007 [PubMed 17350184]).[supplied by OMIM, Mar 2008]

ATP6V0E2 links:

ATP6V0E2-AS1 (HGNC:44180): (ATP6V0E2 antisense RNA 1)

ATP6V0E2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17572859).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V0E2	NM_145230.4	MANE Select	c.65T>C	p.Ile22Thr	missense	Exon 1 of 4	NP_660265.3	Q8NHE4-1
ATP6V0E2	NM_001289990.2		c.65T>C	p.Ile22Thr	missense	Exon 1 of 4	NP_001276919.2	Q8NHE4-3
ATP6V0E2	NM_001100592.3		c.65T>C	p.Ile22Thr	missense	Exon 1 of 3	NP_001094062.2	Q8NHE4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V0E2	ENST00000425642.3	TSL:1 MANE Select	c.65T>C	p.Ile22Thr	missense	Exon 1 of 4	ENSP00000396148.2	Q8NHE4-1
ATP6V0E2	ENST00000421974.7	TSL:1	c.65T>C	p.Ile22Thr	missense	Exon 1 of 3	ENSP00000411672.3	Q8NHE4-2
ATP6V0E2	ENST00000606024.5	TSL:1	c.65T>C	p.Ile22Thr	missense	Exon 1 of 3	ENSP00000475904.1	Q8NHE4-2

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000691

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000344

AC:

AN:

148378

AF XY:

0.000238

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000817

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000945

AC:

1321

AN:

1397620

Hom.:

Cov.:

AF XY:

0.000865

AC XY:

596

AN XY:

689370

show subpopulations

African (AFR)

AF:

0.0000950

AC:

AN:

31564

American (AMR)

AF:

0.000168

AC:

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35718

South Asian (SAS)

AF:

0.00

AC:

AN:

79224

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

48068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00118

AC:

1276

AN:

1078572

Other (OTH)

AF:

0.000604

AC:

AN:

57948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000374

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41584

American (AMR)

AF:

0.000196

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000558

Hom.:

Bravo

AF:

0.000370

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000637

AC:

ExAC

AF:

0.000176

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

0.0033

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.18

MetaSVM

Uncertain

-0.15

PhyloP100

3.0

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.23

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.56

MVP

0.57

MPC

0.70

ClinPred

0.44

GERP RS

5.7

PromoterAI

-0.0064

Neutral

(source)

Varity_R

0.27

gMVP

0.69

Mutation Taster

=60/40

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over