rs2071593

Variant names:

• chr6-31545022-G-A
• rs2071593
• NM_130463.4:c.*386C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31545022-G-A
• chr6-31545022-G-C
• chr6-31545022-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130463.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G2	NM_130463.4	MANE Select	c.*386C>T		3_prime_UTR	Exon 3 of 3	NP_569730.1	O95670-1
	ATP6V1G2	NM_001204078.2		c.*386C>T		3_prime_UTR	Exon 3 of 3	NP_001191007.1	O95670-2
	ATP6V1G2	NM_138282.3		c.*386C>T		3_prime_UTR	Exon 3 of 3	NP_612139.1	O95670-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G2	ENST00000303892.10	TSL:1 MANE Select	c.*386C>T		3_prime_UTR	Exon 3 of 3	ENSP00000302194.5	O95670-1
	ATP6V1G2	ENST00000376151.4	TSL:1	c.*386C>T		3_prime_UTR	Exon 3 of 3	ENSP00000365321.4	O95670-2
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.183+1087C>T		intron	N/A	ENSP00000365356.1	F2Z307

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

African (AFR) AF: 0.0439 AC: 309 AN: 7044

American (AMR) AF: 0.0471 AC: 453 AN: 9616

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 592 AN: 6340

East Asian (EAS) AF: 0.112 AC: 1343 AN: 11960

South Asian (SAS) AF: 0.155 AC: 5290 AN: 34222

European-Finnish (FIN) AF: 0.190 AC: 1922 AN: 10096

Middle Eastern (MID) AF: 0.135 AC: 130 AN: 966

European-Non Finnish (NFE) AF: 0.0717 AC: 9472 AN: 132114

Other (OTH) AF: 0.0854 AC: 1026 AN: 12020

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

African (AFR) AF: 0.0530 AC: 2203 AN: 41546

American (AMR) AF: 0.0580 AC: 888 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.104 AC: 541 AN: 5188

South Asian (SAS) AF: 0.170 AC: 820 AN: 4830

European-Finnish (FIN) AF: 0.235 AC: 2484 AN: 10586

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5081 AN: 68018

Other (OTH) AF: 0.0720 AC: 152 AN: 2110

Alfa AF: 0.0743 Hom.: 1950

Bravo AF: 0.0645

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		-0.23
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: rs2071593; hg19: chr6-31512799; COSMIC: COSV107336001; COSMIC: COSV107336001;