rs2071593

Positions:

• chr6-31545022-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130463.4(ATP6V1G2):​c.*386C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 376,636 control chromosomes in the GnomAD database, including 2,030 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 0.083 (757 hom., cov: 32)
  • Exomes 𝑓: 0.092 (1273 hom.)
• Consequence: ATP6V1G2 NM_130463.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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]

ATP6V1G2-DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.*386C>T		3_prime_UTR_variant	3/3	ENST00000303892.10	NP_569730.1
ATP6V1G2	NM_001204078.2	c.*386C>T		3_prime_UTR_variant	3/3		NP_001191007.1
ATP6V1G2	NM_138282.3	c.*386C>T		3_prime_UTR_variant	3/3		NP_612139.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+1087C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.*386C>T		3_prime_UTR_variant	3/3	1	NM_130463.4	ENSP00000302194.5
ATP6V1G2-DDX39B	ENST00000376185.5	n.183+1087C>T		intron_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12618 AN: 152140 Hom.: 756 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0915 AC: 20537 AN: 224378 Hom.: 1273 Cov.: 0 AF XY: 0.0978 AC XY: 11755 AN XY: 120240

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.0471

Gnomad4 ASJ exome AF: 0.0934

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.0717

Gnomad4 OTH exome AF: 0.0854

GnomAD4 genome AF: 0.0830 AC: 12631 AN: 152258 Hom.: 757 Cov.: 32 AF XY: 0.0925 AC XY: 6888 AN XY: 74444

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0776 Hom.: 983

Bravo AF: 0.0645

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs2071593; hg19: chr6-31512799;