Genetic Variant ATP6V1G1:p.Ser70Arg (chr9-114597594-A-C) – 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_004888.4(ATP6V1G1):c.208A>C(p.Ser70Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000728 in 1,373,088 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: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ATP6V1G1
NM_004888.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Publications

0 publications found

Variant links:

Genes affected

ATP6V1G1 (HGNC:864): (ATPase H+ transporting V1 subunit G1) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of three V1 domain G subunit proteins. Pseudogenes of this gene have been characterized. [provided by RefSeq, Jul 2008]

ATP6V1G1 links:

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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=0.1325784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004888.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G1	NM_004888.4	MANE Select	c.208A>C	p.Ser70Arg	missense	Exon 3 of 3	NP_004879.1	O75348

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V1G1	ENST00000374050.4	TSL:1 MANE Select	c.208A>C	p.Ser70Arg	missense	Exon 3 of 3	ENSP00000363162.3	O75348
ATP6V1G1	ENST00000928169.1		c.220A>C	p.Ser74Arg	missense	Exon 3 of 3	ENSP00000598228.1
ATP6V1G1	ENST00000679150.1		c.290A>C	p.Gln97Pro	missense	Exon 4 of 4	ENSP00000503343.1	A0A7I2V375

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

194630

AF XY:

0.00000936

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.28e-7

AC:

AN:

1373088

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29014

American (AMR)

AF:

0.00

AC:

AN:

29798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23116

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35164

South Asian (SAS)

AF:

0.00

AC:

AN:

72928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5434

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069870

Other (OTH)

AF:

0.00

AC:

AN:

56354

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

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

Cov.:

ExAC

AF:

0.0000165

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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.64

M_CAP

Benign

0.0033

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PhyloP100

4.5

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.12

Sift

Benign

0.063

Sift4G

Benign

0.28

Polyphen

0.0020

Vest4

0.14

MutPred

0.48

Gain of catalytic residue at S70 (P = 0.0201)

MVP

0.43

MPC

0.32

ClinPred

0.52

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.38

Mutation Taster

=55/45

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over