12-123719285-G-A

Position:

• chr12-123719285-G-A

Variant summary

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

The NM_012463.4(ATP6V0A2):​c.196+584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,236 control chromosomes in the GnomAD database, including 68,834 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 0.95 (68834 hom., cov: 32)
• Consequence: ATP6V0A2 NM_012463.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4	c.196+584G>A		intron_variant		ENST00000330342.8	NP_036595.2
LOC105370042	XR_945477.4	n.82-3722C>T		intron_variant, non_coding_transcript_variant
ATP6V0A2	XM_024448910.2	c.196+584G>A		intron_variant			XP_024304678.1
LOC105370042	XR_945478.4	n.82-3722C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8	c.196+584G>A		intron_variant		1	NM_012463.4	ENSP00000332247	P1
	ENST00000652313.1	n.161-3722C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144513 AN: 152118 Hom.: 68779 Cov.: 32

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.970

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

GnomAD4 genome AF: 0.950 AC: 144626 AN: 152236 Hom.: 68834 Cov.: 32 AF XY: 0.948 AC XY: 70534 AN XY: 74416

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.969

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.971

Alfa AF: 0.936 Hom.: 87427

Bravo AF: 0.960

Asia WGS AF: 0.987 AC: 3432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.50

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: rs6488898; hg19: chr12-124203832;