chr9-114597705-C-T

Variant names:

• chr9-114597705-C-T
• rs540425306
• NM_004888.4:c.319C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004888.4(ATP6V1G1):​c.319C>T​(p.Arg107Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000555 in 1,584,268 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 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: ATP6V1G1 NM_004888.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• Publications: 1 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06568354).

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.319C>T	p.Arg107Trp	missense	Exon 3 of 3	NP_004879.1	O75348

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G1	ENST00000374050.4	TSL:1 MANE Select	c.319C>T	p.Arg107Trp	missense	Exon 3 of 3	ENSP00000363162.3	O75348
	ATP6V1G1	ENST00000928169.1		c.331C>T	p.Arg111Trp	missense	Exon 3 of 3	ENSP00000598228.1
	ATP6V1G1	ENST00000679150.1		c.*104C>T		3_prime_UTR	Exon 4 of 4	ENSP00000503343.1	A0A7I2V375

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152078 Hom.: 0 Cov.: 31

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: 0.000415

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000102 AC: 23 AN: 225556 AF XY: 0.000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000379

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000989

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000524 AC: 75 AN: 1432072 Hom.: 0 Cov.: 30 AF XY: 0.0000576 AC XY: 41 AN XY: 712248

African (AFR) AF: 0.00 AC: 0 AN: 31484

American (AMR) AF: 0.0000533 AC: 2 AN: 37540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 37580

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81362

European-Finnish (FIN) AF: 0.00115 AC: 61 AN: 53062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1100758

Other (OTH) AF: 0.0000507 AC: 3 AN: 59204

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152196 Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6 AN XY: 74418

African (AFR) AF: 0.00 AC: 0 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.000944 AC: 10 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000652 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.7
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.024	B
Vest4		0.34
MVP		0.77
MPC		0.29
ClinPred		0.30	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Varity_R		0.68
gMVP		0.57
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs540425306; hg19: chr9-117359985;