Genetic Variant NM_004888.4:c.142C>T (chr9-114592611-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004888.4(ATP6V1G1):c.142C>T(p.Arg48Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000425 in 1,578,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ATP6V1G1
NM_004888.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

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 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.771

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.142C>T	p.Arg48Cys	missense	Exon 2 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.142C>T	p.Arg48Cys	missense	Exon 2 of 3	ENSP00000363162.3	O75348
ATP6V1G1	ENST00000928169.1		c.154C>T	p.Arg52Cys	missense	Exon 2 of 3	ENSP00000598228.1
ATP6V1G1	ENST00000679150.1		c.142C>T	p.Arg48Cys	missense	Exon 2 of 4	ENSP00000503343.1	A0A7I2V375

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152128

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:

0.00633

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000660

AC:

AN:

196898

AF XY:

0.0000574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000553

Gnomad NFE exome

AF:

0.0000715

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000435

AC:

AN:

1425846

Hom.:

Cov.:

AF XY:

0.0000425

AC XY:

AN XY:

705414

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32766

American (AMR)

AF:

0.000253

AC:

AN:

39586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25396

East Asian (EAS)

AF:

0.00

AC:

AN:

38298

South Asian (SAS)

AF:

0.00

AC:

AN:

81170

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

51138

Middle Eastern (MID)

AF:

0.000745

AC:

AN:

5366

European-Non Finnish (NFE)

AF:

0.0000412

AC:

AN:

1093022

Other (OTH)

AF:

0.0000169

AC:

AN:

59104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000328

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41532

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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:

0.0000413

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000415

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.67

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

3.6

PhyloP100

7.5

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.44

Sift

Benign

0.091

Sift4G

Benign

0.10

Polyphen

0.024

Vest4

0.76

MutPred

0.72

Loss of MoRF binding (P = 0.0133)

MVP

0.74

MPC

0.41

ClinPred

0.60

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.64

Mutation Taster

=34/66

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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