rs1139789

Variant names:

• chr12-123724785-T-C
• rs1139789
• NM_012463.4:c.426T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-123724785-T-C
• chr12-123724785-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012463.4(ATP6V0A2):​c.426T>C​(p.Asn142Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,609,970 control chromosomes in the GnomAD database, including 337,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34045 hom., cov: 31)
  • Exomes 𝑓: 0.64 (303029 hom.)
• Consequence: ATP6V0A2 NM_012463.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -4.07

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-123724785-T-C is Benign according to our data. Variant chr12-123724785-T-C is described in ClinVar as [Benign]. Clinvar id is 95523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123724785-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-4.07 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
ATP6V0A2	NM_012463.4	c.426T>C	p.Asn142Asn	synonymous_variant	Exon 4 of 20	ENST00000330342.8	NP_036595.2
ATP6V0A2	XM_024448911.2	c.2T>C	p.Met1?	start_lost	Exon 1 of 16		XP_024304679.1
ATP6V0A2	XM_024448910.2	c.426T>C	p.Asn142Asn	synonymous_variant	Exon 4 of 19		XP_024304678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A2	ENST00000330342.8	c.426T>C	p.Asn142Asn	synonymous_variant	Exon 4 of 20	1	NM_012463.4	ENSP00000332247.2

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101003 AN: 151328 Hom.: 34002 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.672

GnomAD3 exomes AF: 0.686 AC: 172482 AN: 251346 Hom.: 60402 AF XY: 0.677 AC XY: 92005 AN XY: 135840

Gnomad AFR exome AF: 0.689

Gnomad AMR exome AF: 0.801

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.947

Gnomad SAS exome AF: 0.664

Gnomad FIN exome AF: 0.673

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.641 AC: 934233 AN: 1458526 Hom.: 303029 Cov.: 39 AF XY: 0.641 AC XY: 464933 AN XY: 725758

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.659

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.668 AC: 101103 AN: 151444 Hom.: 34045 Cov.: 31 AF XY: 0.671 AC XY: 49648 AN XY: 73940

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.677

Alfa AF: 0.645 Hom.: 17120

Bravo AF: 0.677

Asia WGS AF: 0.818 AC: 2840 AN: 3478

EpiCase AF: 0.621

EpiControl AF: 0.621

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 20, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 11, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cutis laxa with osteodystrophy Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Wrinkly skin syndrome Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ALG9 congenital disorder of glycosylation Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.033
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1139789; hg19: chr12-124209332; COSMIC: COSV57749344; COSMIC: COSV57749344;