rs201620814

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001183.6(ATP6AP1):c.43C>T(p.Arg15Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,147,136 control chromosomes in the GnomAD database, including 4 homozygotes. There are 381 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R15R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., 17 hem., cov: 25)

Exomes 𝑓: 0.00096 ( 3 hom. 364 hem. )

Consequence

ATP6AP1
NM_001183.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.111

Publications

1 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065576136).

BP6

Variant X-154428735-C-T is Benign according to our data. Variant chrX-154428735-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 595205.

BS2

High Hemizygotes in GnomAd4 at 17 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001183.6. 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
	ATP6AP1	NM_001183.6	MANE Select	c.43C>T	p.Arg15Trp	missense	Exon 1 of 10	NP_001174.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6AP1	ENST00000369762.7	TSL:1 MANE Select	c.43C>T	p.Arg15Trp	missense	Exon 1 of 10	ENSP00000358777.2	Q15904
ATP6AP1	ENST00000945275.1		c.43C>T	p.Arg15Trp	missense	Exon 1 of 11	ENSP00000615334.1
ATP6AP1	ENST00000862438.1		c.43C>T	p.Arg15Trp	missense	Exon 1 of 10	ENSP00000532497.1

Frequencies

GnomAD3 genomes

AF:

0.000705

AC:

AN:

113468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000276

Gnomad ASJ

AF:

0.00150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00349

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00114

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00120

AC:

101

AN:

84020

AF XY:

0.00182

show subpopulations

Gnomad AFR exome

AF:

0.000349

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00316

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000485

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000963

AC:

995

AN:

1033620

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

364

AN XY:

335224

show subpopulations

African (AFR)

AF:

0.0000446

AC:

AN:

22441

American (AMR)

AF:

0.0000375

AC:

AN:

26677

Ashkenazi Jewish (ASJ)

AF:

0.00282

AC:

AN:

18078

East Asian (EAS)

AF:

0.00

AC:

AN:

25158

South Asian (SAS)

AF:

0.00388

AC:

190

AN:

49031

European-Finnish (FIN)

AF:

0.000266

AC:

AN:

30081

Middle Eastern (MID)

AF:

0.000253

AC:

AN:

3951

European-Non Finnish (NFE)

AF:

0.000846

AC:

689

AN:

814481

Other (OTH)

AF:

0.00124

AC:

AN:

43722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.000705

AC:

AN:

113516

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

AN XY:

35666

show subpopulations

African (AFR)

AF:

0.0000638

AC:

AN:

31350

American (AMR)

AF:

0.000276

AC:

AN:

10884

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3575

South Asian (SAS)

AF:

0.00350

AC:

AN:

2854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6355

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00114

AC:

AN:

53379

Other (OTH)

AF:

0.00

AC:

AN:

1555

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00155

Hom.:

Bravo

AF:

0.000627

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000965

AC:

ExAC

AF:

0.00102

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

ALG2-congenital disorder of glycosylation (1)

ATP6AP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0066

PhyloP100

-0.11

PROVEAN

Benign

-1.2

Sift

Uncertain

0.029

Sift4G

Uncertain

0.013

Vest4

0.12

MVP

0.13

GERP RS

0.78

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.051

gMVP

0.29

Mutation Taster

=37/163

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

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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