Genetic Variant ATP6V0E2:c.-17G>A (chr7-149874049-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145230.4(ATP6V0E2):c.-17G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,549,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ATP6V0E2
NM_145230.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1255152).

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	Effect	Exon Rank	Protein	UniProt
ATP6V0E2	NM_145230.4	MANE Select	c.-17G>A	5_prime_UTR	Exon 1 of 4	NP_660265.3	Q8NHE4-1
ATP6V0E2	NM_001289990.2		c.-17G>A	5_prime_UTR	Exon 1 of 4	NP_001276919.2	Q8NHE4-3
ATP6V0E2	NM_001100592.3		c.-17G>A	5_prime_UTR	Exon 1 of 3	NP_001094062.2	Q8NHE4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP6V0E2	ENST00000425642.3	TSL:1 MANE Select	c.-17G>A	5_prime_UTR	Exon 1 of 4	ENSP00000396148.2	Q8NHE4-1
ATP6V0E2	ENST00000421974.7	TSL:1	c.-17G>A	5_prime_UTR	Exon 1 of 3	ENSP00000411672.3	Q8NHE4-2
ATP6V0E2	ENST00000606024.5	TSL:1	c.-17G>A	5_prime_UTR	Exon 1 of 3	ENSP00000475904.1	Q8NHE4-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000337

AC:

AN:

148266

AF XY:

0.0000377

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000644

AC:

AN:

1397430

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

689280

show subpopulations

African (AFR)

AF:

0.000190

AC:

AN:

31576

American (AMR)

AF:

0.0000841

AC:

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35720

South Asian (SAS)

AF:

0.00

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078594

Other (OTH)

AF:

0.00

AC:

AN:

57946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000170

AC:

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

0.23

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

PhyloP100

1.4

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.1

REVEL

Benign

0.064

Sift

Uncertain

0.013

Sift4G

Uncertain

0.026

Polyphen

0.90

Vest4

0.40

MutPred

0.49

Loss of glycosylation at S41 (P = 0.0972)

MVP

0.30

MPC

0.28

ClinPred

0.039

GERP RS

3.4

PromoterAI

0.31

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.69

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over