rs12636577

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001690.4(ATP6V1A):c.-13-81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 654,768 control chromosomes in the GnomAD database, including 40,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8529 hom., cov: 32)

Exomes 𝑓: 0.35 ( 31652 hom. )

Consequence

ATP6V1A
NM_001690.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.267

Publications

5 publications found

Variant links:

Genes affected

ATP6V1A (HGNC:851): (ATPase H+ transporting V1 subunit A) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain A subunit isoforms and is found in all tissues. Transcript variants derived from alternative polyadenylation exist. [provided by RefSeq, Jul 2008]

ATP6V1A Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy 93
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal recessive cutis laxa type 2D
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Genomics England PanelApp, Ambry Genetics
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive cutis laxa type 2, classic type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATP6V1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 3-113778660-A-G is Benign according to our data. Variant chr3-113778660-A-G is described in ClinVar as Benign. ClinVar VariationId is 1268535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ATP6V1A	NM_001690.4 link	c.-13-81A>G	intron_variant	Intron 1 of 14	ENST00000273398.8	NP_001681.2
ATP6V1A	XM_047448305.1 link	c.-13-81A>G	intron_variant	Intron 1 of 14		XP_047304261.1
ATP6V1A	XM_047448306.1 link	c.-13-81A>G	intron_variant	Intron 2 of 15		XP_047304262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1A	ENST00000273398.8 link	c.-13-81A>G		intron_variant	Intron 1 of 14	1	NM_001690.4	ENSP00000273398.3
ATP6V1A	ENST00000703904.2 link	c.-13-81A>G		intron_variant	Intron 2 of 15			ENSP00000515542.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50476

AN:

151908

Hom.:

8532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.348

AC:

174975

AN:

502742

Hom.:

31652

AF XY:

0.344

AC XY:

90344

AN XY:

262424

show subpopulations

African (AFR)

AF:

0.309

AC:

3406

AN:

11010

American (AMR)

AF:

0.228

AC:

2738

AN:

12032

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

3119

AN:

12570

East Asian (EAS)

AF:

0.406

AC:

10583

AN:

26054

South Asian (SAS)

AF:

0.212

AC:

5949

AN:

28114

European-Finnish (FIN)

AF:

0.462

AC:

18549

AN:

40176

Middle Eastern (MID)

AF:

0.285

AC:

538

AN:

1890

European-Non Finnish (NFE)

AF:

0.353

AC:

121711

AN:

344932

Other (OTH)

AF:

0.323

AC:

8382

AN:

25964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5404

10808

16213

21617

27021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2094

4188

6282

8376

10470

<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:

0.332

AC:

50476

AN:

152026

Hom.:

8529

Cov.:

AF XY:

0.332

AC XY:

24694

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.305

AC:

12658

AN:

41470

American (AMR)

AF:

0.250

AC:

3813

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

857

AN:

3470

East Asian (EAS)

AF:

0.364

AC:

1882

AN:

5174

South Asian (SAS)

AF:

0.214

AC:

1030

AN:

4822

European-Finnish (FIN)

AF:

0.452

AC:

4760

AN:

10538

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24333

AN:

67962

Other (OTH)

AF:

0.306

AC:

647

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1743

3487

5230

6974

8717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.345

Hom.:

1191

Bravo

AF:

0.317

Asia WGS

AF:

0.252

AC:

872

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 10, 2021

GeneDx

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

-0.66

CADD

Benign

2.8

(source)

DANN

Benign

0.91

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over