NM_130463.4:c.*465C>G

Variant names:

• chr6-31544943-G-C
• rs2071594
• NM_130463.4:c.*465C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130463.4(ATP6V1G2):​c.*465C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 360,030 control chromosomes in the GnomAD database, including 24,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11611 hom., cov: 32)
  • Exomes 𝑓: 0.34 (12594 hom.)
• Consequence: ATP6V1G2 NM_130463.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876
• Publications: 35 publications found

Genes affected

ATP6V1G2 (HGNC:862): (ATPase H+ transporting V1 subunit G2) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent 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 and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.*465C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000303892.10	NP_569730.1
ATP6V1G2	NM_001204078.2	c.*465C>G		3_prime_UTR_variant	Exon 3 of 3		NP_001191007.1
ATP6V1G2	NM_138282.3	c.*465C>G		3_prime_UTR_variant	Exon 3 of 3		NP_612139.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+1166C>G		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.*465C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_130463.4	ENSP00000302194.5
ATP6V1G2-DDX39B	ENST00000376185.5	n.183+1166C>G		intron_variant	Intron 2 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58188 AN: 151860 Hom.: 11599 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.343 AC: 71447 AN: 208052 Hom.: 12594 Cov.: 0 AF XY: 0.337 AC XY: 38843 AN XY: 115186

African (AFR) AF: 0.505 AC: 2815 AN: 5572

American (AMR) AF: 0.346 AC: 3980 AN: 11488

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 1298 AN: 4780

East Asian (EAS) AF: 0.498 AC: 4292 AN: 8610

South Asian (SAS) AF: 0.293 AC: 12069 AN: 41222

European-Finnish (FIN) AF: 0.331 AC: 2938 AN: 8886

Middle Eastern (MID) AF: 0.422 AC: 927 AN: 2196

European-Non Finnish (NFE) AF: 0.344 AC: 39628 AN: 115158

Other (OTH) AF: 0.345 AC: 3500 AN: 10140

GnomAD4 genome AF: 0.383 AC: 58239 AN: 151978 Hom.: 11611 Cov.: 32 AF XY: 0.379 AC XY: 28158 AN XY: 74282

African (AFR) AF: 0.502 AC: 20794 AN: 41410

American (AMR) AF: 0.348 AC: 5311 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 873 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2452 AN: 5178

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4826

European-Finnish (FIN) AF: 0.303 AC: 3200 AN: 10568

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23068 AN: 67938

Other (OTH) AF: 0.354 AC: 748 AN: 2114

Alfa AF: 0.325 Hom.: 4430

Bravo AF: 0.392

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs2071594; hg19: chr6-31512720; COSMIC: COSV107336000; COSMIC: COSV107336000;