rs1399961

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012463.4(ATP6V0A2):c.471T>C(p.Ser157Ser) 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
NM_012463.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.67

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive cutis laxa type 2A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
wrinkly skin syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp
autosomal recessive cutis laxa type 2, classic type
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ATP6V0A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 95525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012463.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A2	NM_012463.4	MANE Select	c.471T>C	p.Ser157Ser	synonymous	Exon 5 of 20	NP_036595.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V0A2	ENST00000330342.8	TSL:1 MANE Select	c.471T>C	p.Ser157Ser	synonymous	Exon 5 of 20	ENSP00000332247.2	Q9Y487
ATP6V0A2	ENST00000613625.5	TSL:1	c.471T>C	p.Ser157Ser	synonymous	Exon 5 of 9	ENSP00000482236.1	Q8TBM3
ATP6V0A2	ENST00000540368.6	TSL:1	n.502T>C		non_coding_transcript_exon	Exon 5 of 18

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

GnomAD2 exomes

AF:

0.683

AC:

171671

AN:

251420

AF XY:

0.674

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 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

African (AFR)

AF:

0.675

AC:

22570

AN:

33426

American (AMR)

AF:

0.795

AC:

35550

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

17102

AN:

26120

East Asian (EAS)

AF:

0.955

AC:

37891

AN:

39686

South Asian (SAS)

AF:

0.659

AC:

56806

AN:

86212

European-Finnish (FIN)

AF:

0.675

AC:

36028

AN:

53406

Middle Eastern (MID)

AF:

0.634

AC:

3653

AN:

5762

European-Non Finnish (NFE)

AF:

0.609

AC:

675848

AN:

1110296

Other (OTH)

AF:

0.655

AC:

39486

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15919

31838

47758

63677

79596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18402

36804

55206

73608

92010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.665

AC:

101062

AN:

152006

Hom.:

33933

Cov.:

AF XY:

0.669

AC XY:

49739

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.679

AC:

28152

AN:

41440

American (AMR)

AF:

0.742

AC:

11336

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

2264

AN:

3468

East Asian (EAS)

AF:

0.948

AC:

4907

AN:

5178

South Asian (SAS)

AF:

0.681

AC:

3282

AN:

4818

European-Finnish (FIN)

AF:

0.678

AC:

7157

AN:

10554

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41885

AN:

67964

Other (OTH)

AF:

0.675

AC:

1422

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1732

3464

5195

6927

8659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.629

Hom.:

54096

Bravo

AF:

0.673

Asia WGS

AF:

0.819

AC:

2844

AN:

3478

EpiCase

AF:

0.614

EpiControl

AF:

0.615

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Cutis laxa with osteodystrophy (2)

ALG9 congenital disorder of glycosylation (1)

not provided (1)

Wrinkly skin syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.58

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over