12-123726235-T-C

Position:

chr12-123726235-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000330342.8(ATP6V0A2):c.471T>C(p.Ser157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,611,954 control chromosomes in the GnomAD database, including 330,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33933 hom., cov: 31)

Exomes 𝑓: 0.63 ( 296883 hom. )

Consequence

ATP6V0A2
ENST00000330342.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.67

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-123726235-T-C is Benign according to our data. Variant chr12-123726235-T-C is described in ClinVar as [Benign]. Clinvar id is 95525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123726235-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATP6V0A2	NM_012463.4 linkuse as main transcript	c.471T>C	p.Ser157=	synonymous_variant	5/20	ENST00000330342.8	NP_036595.2
ATP6V0A2	XM_024448910.2 linkuse as main transcript	c.471T>C	p.Ser157=	synonymous_variant	5/19		XP_024304678.1
ATP6V0A2	XM_024448911.2 linkuse as main transcript	c.8+1444T>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.471T>C	p.Ser157=	synonymous_variant	5/20	1	NM_012463.4	ENSP00000332247	P1

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100960

AN:

151888

Hom.:

33889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.948

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.670

GnomAD3 exomes

AF:

0.683

AC:

171671

AN:

251420

Hom.:

59878

AF XY:

0.674

AC XY:

91570

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.800

Gnomad ASJ exome

AF:

0.655

Gnomad EAS exome

AF:

0.947

Gnomad SAS exome

AF:

0.664

Gnomad FIN exome

AF:

0.671

Gnomad NFE exome

AF:

0.615

Gnomad OTH exome

AF:

0.657

GnomAD4 exome

AF:

0.634

AC:

924934

AN:

1459948

Hom.:

296883

Cov.:

AF XY:

0.634

AC XY:

460321

AN XY:

726362

show subpopulations

Gnomad4 AFR exome

AF:

0.675

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.655

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:

0.665

AC:

101062

AN:

152006

Hom.:

33933

Cov.:

AF XY:

0.669

AC XY:

49739

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.679

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.653

Gnomad4 EAS

AF:

0.948

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.616

Gnomad4 OTH

AF:

0.675

Alfa

AF:

0.628

Hom.:

46317

Bravo

AF:

0.673

Asia WGS

AF:

0.819

AC:

2844

AN:

3478

EpiCase

AF:

0.614

EpiControl

AF:

0.615

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 25, 2012	- -
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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Cutis laxa with osteodystrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

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

-0.90

CADD

Benign

1.2

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 50

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