rs754577497

Variant names:

• chr9-114597729-C-A
• NM_004888.4:c.343C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-114597729-C-A
• chr9-114597729-C-G
• chr9-114597729-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004888.4(ATP6V1G1):​c.343C>A​(p.Arg115Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R115C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ATP6V1G1 NM_004888.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1G1	NM_004888.4	c.343C>A	p.Arg115Ser	missense_variant	Exon 3 of 3	ENST00000374050.4	NP_004879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G1	ENST00000374050.4	c.343C>A	p.Arg115Ser	missense_variant	Exon 3 of 3	1	NM_004888.4	ENSP00000363162.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432232 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 712408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.85	P
Vest4		0.74
MutPred		0.51		Loss of methylation at R115 (P = 0.0223);
MVP		0.73
MPC		0.52
ClinPred		0.97	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-117360009;