X-154428787-TGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001183.6(ATP6AP1):c.111_116dupGGCGGC(p.Ala38_Ala39dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,124,353 control chromosomes in the GnomAD database, including 1,267 homozygotes. There are 3,562 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 735 hom., 2048 hem., cov: 21)

Exomes 𝑓: 0.0066 ( 532 hom. 1514 hem. )

Consequence

ATP6AP1
NM_001183.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.146

Publications

3 publications found

Variant links:

COSMIC-nc: COSV62341026

Genes affected

ATP6AP1 (HGNC:868): (ATPase H+ transporting accessory protein 1) This gene encodes a component of a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Vacuolar ATPase (V-ATPase) is comprised of a cytosolic V1 (site of the ATP catalytic site) and a transmembrane V0 domain. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. The encoded protein of this gene may assist in the V-ATPase-mediated acidification of neuroendocrine secretory granules. This protein may also play a role in early development. [provided by RefSeq, Aug 2013]

ATP6AP1 links:

ATP6AP1-DT (HGNC:25138): (ATP6AP1 divergent transcript)

ATP6AP1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-154428787-T-TGGCGGC is Benign according to our data. Variant chrX-154428787-T-TGGCGGC is described in ClinVar as [Benign]. Clinvar id is 1165872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6 link	c.111_116dupGGCGGC	p.Ala38_Ala39dup	disruptive_inframe_insertion	Exon 1 of 10	ENST00000369762.7	NP_001174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1	ENST00000369762.7 link	c.111_116dupGGCGGC	p.Ala38_Ala39dup	disruptive_inframe_insertion	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2		Q15904

Frequencies

GnomAD3 genomes

AF:

0.0710

AC:

7960

AN:

112046

Hom.:

735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0271

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.000709

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00851

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0568

GnomAD2 exomes

AF:

0.00470

AC:

256

AN:

54469

AF XY:

0.00220

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.00733

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000656

Gnomad OTH exome

AF:

0.00421

GnomAD4 exome

AF:

0.00662

AC:

6697

AN:

1012267

Hom.:

532

Cov.:

AF XY:

0.00465

AC XY:

1514

AN XY:

325735

show subpopulations

African (AFR)

AF:

0.249

AC:

5126

AN:

20599

American (AMR)

AF:

0.0107

AC:

243

AN:

22637

Ashkenazi Jewish (ASJ)

AF:

0.000177

AC:

AN:

16951

East Asian (EAS)

AF:

0.000249

AC:

AN:

24117

South Asian (SAS)

AF:

0.000498

AC:

AN:

46151

European-Finnish (FIN)

AF:

0.0000351

AC:

AN:

28515

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

3620

European-Non Finnish (NFE)

AF:

0.000595

AC:

480

AN:

806952

Other (OTH)

AF:

0.0182

AC:

778

AN:

42725

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

260

521

781

1042

1302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0712

AC:

7978

AN:

112086

Hom.:

735

Cov.:

AF XY:

0.0594

AC XY:

2048

AN XY:

34460

show subpopulations

African (AFR)

AF:

0.247

AC:

7539

AN:

30541

American (AMR)

AF:

0.0270

AC:

292

AN:

10797

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.000282

AC:

AN:

3542

South Asian (SAS)

AF:

0.000356

AC:

AN:

2811

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6209

Middle Eastern (MID)

AF:

0.00935

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

53116

Other (OTH)

AF:

0.0561

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

217

434

651

868

1085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00185

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 19, 2021

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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X-154428787-TGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGC

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