rs2071594

Variant names:

• chr6-31544943-G-A
• rs2071594
• NM_130463.4:c.*465C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31544943-G-A
• chr6-31544943-G-C
• chr6-31544943-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130463.4(ATP6V1G2):​c.*465C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP6V1G2 NM_130463.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876
• Publications: 35 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.*465C>T		3_prime_UTR	Exon 3 of 3	NP_569730.1	O95670-1
	ATP6V1G2	NM_001204078.2		c.*465C>T		3_prime_UTR	Exon 3 of 3	NP_001191007.1	O95670-2
	ATP6V1G2	NM_138282.3		c.*465C>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.*465C>T		3_prime_UTR	Exon 3 of 3	ENSP00000302194.5	O95670-1
	ATP6V1G2	ENST00000376151.4	TSL:1	c.*465C>T		3_prime_UTR	Exon 3 of 3	ENSP00000365321.4	O95670-2
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.183+1166C>T		intron	N/A	ENSP00000365356.1	F2Z307

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 208544 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 115462

African (AFR) AF: 0.00 AC: 0 AN: 5580

American (AMR) AF: 0.00 AC: 0 AN: 11510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4794

East Asian (EAS) AF: 0.00 AC: 0 AN: 8624

South Asian (SAS) AF: 0.00 AC: 0 AN: 41308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2200

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 115432

Other (OTH) AF: 0.00 AC: 0 AN: 10164

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.28
PhyloP100		0.88

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: rs2071594; hg19: chr6-31512720;