dbSNP rs28497482: ATP6AP1:p.Arg15Arg (chrX-154428737-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001183.6(ATP6AP1):c.45G>A(p.Arg15Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,146,269 control chromosomes in the GnomAD database, including 5,214 homozygotes. There are 42,749 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 473 hom., 3776 hem., cov: 25)

Exomes 𝑓: 0.11 ( 4741 hom. 38973 hem. )

Consequence

ATP6AP1
NM_001183.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.519

Publications

10 publications found

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:

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

ATP6AP1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant X-154428737-G-A is Benign according to our data. Variant chrX-154428737-G-A is described in ClinVar as [Benign]. Clinvar id is 770830.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.519 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6 link	c.45G>A	p.Arg15Arg	synonymous_variant	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.45G>A	p.Arg15Arg	synonymous_variant	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2		Q15904

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

11909

AN:

113143

Hom.:

465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.00875

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0600

Gnomad EAS

AF:

0.0617

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0464

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0930

GnomAD4 exome

AF:

0.115

AC:

118410

AN:

1033077

Hom.:

4741

Cov.:

AF XY:

0.116

AC XY:

38973

AN XY:

335163

show subpopulations

African (AFR)

AF:

0.0854

AC:

1912

AN:

22390

American (AMR)

AF:

0.141

AC:

3761

AN:

26605

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

1151

AN:

18056

East Asian (EAS)

AF:

0.0744

AC:

1869

AN:

25135

South Asian (SAS)

AF:

0.167

AC:

8170

AN:

49013

European-Finnish (FIN)

AF:

0.148

AC:

4421

AN:

29847

Middle Eastern (MID)

AF:

0.0540

AC:

213

AN:

3946

European-Non Finnish (NFE)

AF:

0.113

AC:

92017

AN:

814364

Other (OTH)

AF:

0.112

AC:

4896

AN:

43721

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

5332

10663

15995

21326

26658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.105

AC:

11928

AN:

113192

Hom.:

473

Cov.:

AF XY:

0.107

AC XY:

3776

AN XY:

35356

show subpopulations

African (AFR)

AF:

0.0914

AC:

2860

AN:

31282

American (AMR)

AF:

0.130

AC:

1409

AN:

10873

Ashkenazi Jewish (ASJ)

AF:

0.0600

AC:

159

AN:

2651

East Asian (EAS)

AF:

0.0608

AC:

216

AN:

3553

South Asian (SAS)

AF:

0.160

AC:

454

AN:

2843

European-Finnish (FIN)

AF:

0.140

AC:

876

AN:

6270

Middle Eastern (MID)

AF:

0.0509

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.108

AC:

5775

AN:

53261

Other (OTH)

AF:

0.104

AC:

162

AN:

1557

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

387

774

1161

1548

1935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.111

Hom.:

982

Bravo

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

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

-0.50

CADD

Benign

8.2

(source)

PhyloP100

0.52

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

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rs28497482

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