chr6-31546087-A-T

Position:

• chr6-31546087-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ATP6V1G2	NM_130463.4	c.183+22T>A		intron_variant		ENST00000303892.10	NP_569730.1
ATP6V1G2	NM_001204078.2	c.105+100T>A		intron_variant			NP_001191007.1
ATP6V1G2	NM_138282.3	c.60+22T>A		intron_variant			NP_612139.1
ATP6V1G2-DDX39B	NR_037853.1	n.472+22T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.183+22T>A		intron_variant		1	NM_130463.4	ENSP00000302194.5
ATP6V1G2-DDX39B	ENST00000376185.5	n.183+22T>A		intron_variant		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

GnomAD3 exomes AF: 0.855 AC: 214953 AN: 251404 Hom.: 92324 AF XY: 0.860 AC XY: 116864 AN XY: 135872

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 SAS exome AF: 0.925

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

Gnomad4 AFR exome AF: 0.885

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.835

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

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.860

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523502; hg19: chr6-31513864;