Variant X-154428787-T-TGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001183.6(ATP6AP1):c.111_116dup(p.Ala40_Ala41dup) variant causes a 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 inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.146

Variant links:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ATP6AP1	NM_001183.6 linkuse as main transcript	c.111_116dup	p.Ala40_Ala41dup	inframe_insertion	1/10	ENST00000369762.7	NP_001174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6AP1	ENST00000369762.7 linkuse as main transcript	c.111_116dup	p.Ala40_Ala41dup	inframe_insertion	1/10	1	NM_001183.6	ENSP00000358777	P1

Frequencies

GnomAD3 genomes

AF:

0.0710

AC:

7960

AN:

112046

Hom.:

735

Cov.:

AF XY:

0.0590

AC XY:

2030

AN XY:

34410

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

GnomAD3 exomes

AF:

0.00470

AC:

256

AN:

54469

Hom.:

AF XY:

0.00220

AC XY:

AN XY:

14567

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 SAS exome

AF:

0.000121

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

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.000177

Gnomad4 EAS exome

AF:

0.000249

Gnomad4 SAS exome

AF:

0.000498

Gnomad4 FIN exome

AF:

0.0000351

Gnomad4 NFE exome

AF:

0.000595

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0712

AC:

7978

AN:

112086

Hom.:

735

Cov.:

AF XY:

0.0594

AC XY:

2048

AN XY:

34460

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.0270

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.000356

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.0561

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 2019	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2021

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

Splicing

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