12-123724805-C-T

Position:

chr12-123724805-C-T

Variant summary

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

The NM_012463.4(ATP6V0A2):c.432+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,606,302 control chromosomes in the GnomAD database, including 330,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33684 hom., cov: 32)

Exomes 𝑓: 0.63 ( 296376 hom. )

Consequence

ATP6V0A2
NM_012463.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.72

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 12-123724805-C-T is Benign according to our data. Variant chr12-123724805-C-T is described in ClinVar as [Benign]. Clinvar id is 95524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123724805-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ATP6V0A2	NM_012463.4 linkuse as main transcript	c.432+14C>T	intron_variant	ENST00000330342.8
ATP6V0A2	XM_024448910.2 linkuse as main transcript	c.432+14C>T	intron_variant
ATP6V0A2	XM_024448911.2 linkuse as main transcript	c.8+14C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0A2	ENST00000330342.8 linkuse as main transcript	c.432+14C>T		intron_variant		1	NM_012463.4	P1

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

100461

AN:

151382

Hom.:

33640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.517

Gnomad AMR

AF:

0.741

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.947

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.668

GnomAD3 exomes

AF:

0.682

AC:

171421

AN:

251178

Hom.:

59750

AF XY:

0.674

AC XY:

91448

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.799

Gnomad ASJ exome

AF:

0.654

Gnomad EAS exome

AF:

0.947

Gnomad SAS exome

AF:

0.664

Gnomad FIN exome

AF:

0.671

Gnomad NFE exome

AF:

0.614

Gnomad OTH exome

AF:

0.657

GnomAD4 exome

AF:

0.634

AC:

921917

AN:

1454802

Hom.:

296376

Cov.:

AF XY:

0.634

AC XY:

458970

AN XY:

724000

show subpopulations

Gnomad4 AFR exome

AF:

0.675

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.654

Gnomad4 EAS exome

AF:

0.955

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.675

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.664

AC:

100563

AN:

151500

Hom.:

33684

Cov.:

AF XY:

0.668

AC XY:

49447

AN XY:

73988

show subpopulations

Gnomad4 AFR

AF:

0.678

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.654

Gnomad4 EAS

AF:

0.948

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.676

Gnomad4 NFE

AF:

0.615

Gnomad4 OTH

AF:

0.673

Alfa

AF:

0.631

Hom.:

45965

Bravo

AF:

0.673

Asia WGS

AF:

0.817

AC:

2839

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 20, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Cutis laxa with osteodystrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Wrinkly skin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ALG9 congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.030

DANN

Benign

0.65

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