6-31544943-G-C

Position:

• chr6-31544943-G-C

Variant summary

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

The NM_130463.4(ATP6V1G2):​c.*465C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 360,030 control chromosomes in the GnomAD database, including 24,205 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 0.38 (11611 hom., cov: 32)
  • Exomes 𝑓: 0.34 (12594 hom.)
• Consequence: ATP6V1G2 NM_130463.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1G2	NM_130463.4	c.*465C>G		3_prime_UTR_variant	3/3	ENST00000303892.10
ATP6V1G2-DDX39B	NR_037853.1	n.472+1166C>G		intron_variant, non_coding_transcript_variant
ATP6V1G2	NM_001204078.2	c.*465C>G		3_prime_UTR_variant	3/3
ATP6V1G2	NM_138282.3	c.*465C>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1G2	ENST00000303892.10	c.*465C>G		3_prime_UTR_variant	3/3	1	NM_130463.4	P1
ATP6V1G2	ENST00000376151.4	c.*465C>G		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58188 AN: 151860 Hom.: 11599 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.343 AC: 71447 AN: 208052 Hom.: 12594 Cov.: 0 AF XY: 0.337 AC XY: 38843 AN XY: 115186

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.383 AC: 58239 AN: 151978 Hom.: 11611 Cov.: 32 AF XY: 0.379 AC XY: 28158 AN XY: 74282

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.354

Alfa AF: 0.325 Hom.: 4430

Bravo AF: 0.392

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.46

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: rs2071594; hg19: chr6-31512720;