6-31546087-A-T

Variant names:

• chr6-31546087-A-T
• rs2523502
• NM_130463.4:c.183+22T>A

Variant summary

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

The NM_130463.4(ATP6V1G2):​c.183+22T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 1,612,888 control chromosomes in the GnomAD database, including 553,444 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 0.85 (54472 hom., cov: 27)
  • Exomes 𝑓: 0.83 (498972 hom.)
• Consequence: ATP6V1G2 NM_130463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 23 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.183+22T>A		intron_variant	Intron 2 of 2	ENST00000303892.10	NP_569730.1
ATP6V1G2	NM_001204078.2	c.105+100T>A		intron_variant	Intron 2 of 2		NP_001191007.1
ATP6V1G2	NM_138282.3	c.60+22T>A		intron_variant	Intron 2 of 2		NP_612139.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+22T>A		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.183+22T>A		intron_variant	Intron 2 of 2	1	NM_130463.4	ENSP00000302194.5
ATP6V1G2-DDX39B	ENST00000376185.5	n.183+22T>A		intron_variant	Intron 2 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128283 AN: 151492 Hom.: 54415 Cov.: 27

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.860

GnomAD2 exomes AF: 0.855 AC: 214953 AN: 251404 AF XY: 0.860

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.944

Gnomad EAS exome AF: 0.931

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.820

Gnomad OTH exome AF: 0.852

GnomAD4 exome AF: 0.825 AC: 1205738 AN: 1461278 Hom.: 498972 Cov.: 41 AF XY: 0.829 AC XY: 602850 AN XY: 726990

African (AFR) AF: 0.885 AC: 29626 AN: 33476

American (AMR) AF: 0.865 AC: 38677 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 24558 AN: 26130

East Asian (EAS) AF: 0.920 AC: 36541 AN: 39700

South Asian (SAS) AF: 0.926 AC: 79868 AN: 86248

European-Finnish (FIN) AF: 0.816 AC: 43587 AN: 53396

Middle Eastern (MID) AF: 0.913 AC: 5263 AN: 5766

European-Non Finnish (NFE) AF: 0.807 AC: 897181 AN: 1111468

Other (OTH) AF: 0.835 AC: 50437 AN: 60372

GnomAD4 genome AF: 0.847 AC: 128397 AN: 151610 Hom.: 54472 Cov.: 27 AF XY: 0.852 AC XY: 63030 AN XY: 74020

African (AFR) AF: 0.877 AC: 36200 AN: 41288

American (AMR) AF: 0.868 AC: 13221 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3264 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4745 AN: 5124

South Asian (SAS) AF: 0.923 AC: 4432 AN: 4800

European-Finnish (FIN) AF: 0.825 AC: 8628 AN: 10454

Middle Eastern (MID) AF: 0.908 AC: 265 AN: 292

European-Non Finnish (NFE) AF: 0.811 AC: 55077 AN: 67934

Other (OTH) AF: 0.860 AC: 1811 AN: 2106

Alfa AF: 0.841 Hom.: 9949

Bravo AF: 0.850

Asia WGS AF: 0.865 AC: 3010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.57
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2523502; hg19: chr6-31513864;