12-123722841-T-G

Position:

• chr12-123722841-T-G

Variant summary

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

The NM_012463.4(ATP6V0A2):​c.294+393T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,538 control chromosomes in the GnomAD database, including 33,779 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 0.66 (33779 hom., cov: 28)
• Consequence: ATP6V0A2 NM_012463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

ATP6V0A2 (HGNC:18481): (ATPase H+ transporting V0 subunit a2) The protein encoded by this gene is a subunit of the vacuolar ATPase (v-ATPase), an heteromultimeric enzyme that is present in intracellular vesicles and in the plasma membrane of specialized cells, and which is essential for the acidification of diverse cellular components. V-ATPase is comprised of a membrane peripheral V(1) domain for ATP hydrolysis, and an integral membrane V(0) domain for proton translocation. The subunit encoded by this gene is a component of the V(0) domain. Mutations in this gene are a cause of both cutis laxa type II and wrinkly skin syndrome. [provided by RefSeq, Jul 2009]

ATP6V0A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4	c.294+393T>G		intron_variant		ENST00000330342.8	NP_036595.2
ATP6V0A2	XM_024448910.2	c.294+393T>G		intron_variant			XP_024304678.1
LOC105370042	XR_945477.4	n.81+169A>C		intron_variant
LOC105370042	XR_945478.4	n.81+169A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8	c.294+393T>G		intron_variant		1	NM_012463.4	ENSP00000332247.2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100566 AN: 151420 Hom.: 33735 Cov.: 28

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.670

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 100668 AN: 151538 Hom.: 33779 Cov.: 28 AF XY: 0.669 AC XY: 49533 AN XY: 74038

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.674

Alfa AF: 0.657 Hom.: 5567

Bravo AF: 0.673

Asia WGS AF: 0.819 AC: 2845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10734905; hg19: chr12-124207388;