Variant chr12-123735508-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012463.4(ATP6V0A2):c.732-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,601,846 control chromosomes in the GnomAD database, including 303,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27895 hom., cov: 30)

Exomes 𝑓: 0.61 ( 275557 hom. )

Consequence

ATP6V0A2
NM_012463.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.16

Variant links:

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 links:

ATP6V0A2 (HGNC:):

ATP6V0A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 12-123735508-T-C is Benign according to our data. Variant chr12-123735508-T-C is described in ClinVar as [Benign]. Clinvar id is 260260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123735508-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4 linkuse as main transcript	c.732-23T>C	intron_variant	ENST00000330342.8	NP_036595.2	Q9Y487
ATP6V0A2	XM_024448910.2 linkuse as main transcript	c.732-23T>C	intron_variant		XP_024304678.1
ATP6V0A2	XM_024448911.2 linkuse as main transcript	c.219-23T>C	intron_variant		XP_024304679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8 linkuse as main transcript	c.732-23T>C		intron_variant		1	NM_012463.4	ENSP00000332247.2		Q9Y487

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

90892

AN:

151700

Hom.:

27861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.946

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.639

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.618

GnomAD3 exomes

AF:

0.651

AC:

163182

AN:

250812

Hom.:

54566

AF XY:

0.643

AC XY:

87252

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.780

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.946

Gnomad SAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.632

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.628

GnomAD4 exome

AF:

0.612

AC:

887091

AN:

1450028

Hom.:

275557

Cov.:

AF XY:

0.612

AC XY:

441669

AN XY:

722086

show subpopulations

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.773

Gnomad4 ASJ exome

AF:

0.622

Gnomad4 EAS exome

AF:

0.954

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.636

Gnomad4 NFE exome

AF:

0.594

Gnomad4 OTH exome

AF:

0.624

GnomAD4 genome

AF:

0.599

AC:

90974

AN:

151818

Hom.:

27895

Cov.:

AF XY:

0.605

AC XY:

44894

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.705

Gnomad4 ASJ

AF:

0.620

Gnomad4 EAS

AF:

0.946

Gnomad4 SAS

AF:

0.651

Gnomad4 FIN

AF:

0.639

Gnomad4 NFE

AF:

0.599

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.608

Hom.:

47361

Bravo

AF:

0.606

Asia WGS

AF:

0.789

AC:

2741

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Wrinkly skin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Cutis laxa with osteodystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.28

DANN

Benign

0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over