NM_130463.4:c.184-44C>T

Variant names:

• chr6-31545625-G-A
• rs2239705
• NM_130463.4:c.184-44C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_130463.4(ATP6V1G2):​c.184-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,594,274 control chromosomes in the GnomAD database, including 24,083 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 0.16 (2263 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21820 hom.)
• Consequence: ATP6V1G2 NM_130463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 51 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.184-44C>T		intron_variant	Intron 2 of 2	ENST00000303892.10	NP_569730.1
ATP6V1G2	NM_001204078.2	c.106-86C>T		intron_variant	Intron 2 of 2		NP_001191007.1
ATP6V1G2	NM_138282.3	c.61-44C>T		intron_variant	Intron 2 of 2		NP_612139.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+484C>T		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.184-44C>T		intron_variant	Intron 2 of 2	1	NM_130463.4	ENSP00000302194.5
ATP6V1G2-DDX39B	ENST00000376185.5	n.183+484C>T		intron_variant	Intron 2 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24659 AN: 152024 Hom.: 2265 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.184 AC: 41711 AN: 226950 AF XY: 0.183

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.0932

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.168 AC: 242360 AN: 1442134 Hom.: 21820 Cov.: 30 AF XY: 0.169 AC XY: 121050 AN XY: 716760

African (AFR) AF: 0.130 AC: 4285 AN: 32922

American (AMR) AF: 0.290 AC: 12157 AN: 41980

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7637 AN: 25242

East Asian (EAS) AF: 0.173 AC: 6849 AN: 39498

South Asian (SAS) AF: 0.159 AC: 13491 AN: 84696

European-Finnish (FIN) AF: 0.0891 AC: 4613 AN: 51772

Middle Eastern (MID) AF: 0.183 AC: 885 AN: 4824

European-Non Finnish (NFE) AF: 0.166 AC: 182611 AN: 1101534

Other (OTH) AF: 0.165 AC: 9832 AN: 59666

GnomAD4 genome AF: 0.162 AC: 24673 AN: 152140 Hom.: 2263 Cov.: 32 AF XY: 0.161 AC XY: 11997 AN XY: 74386

African (AFR) AF: 0.122 AC: 5078 AN: 41488

American (AMR) AF: 0.252 AC: 3855 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3470

East Asian (EAS) AF: 0.158 AC: 817 AN: 5170

South Asian (SAS) AF: 0.148 AC: 714 AN: 4828

European-Finnish (FIN) AF: 0.0885 AC: 938 AN: 10600

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11620 AN: 67984

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.178 Hom.: 11595

Bravo AF: 0.176

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		1.7
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2239705; hg19: chr6-31513402;