Genetic Variant NM_001183.6:c.71C>T (chrX-154428763-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001183.6(ATP6AP1):c.71C>T(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 112,593 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ATP6AP1
NM_001183.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08425167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6 link	c.71C>T	p.Pro24Leu	missense_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.71C>T	p.Pro24Leu	missense_variant	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2		Q15904

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112593

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1022305

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

330363

African (AFR)

AF:

0.00

AC:

AN:

21456

American (AMR)

AF:

0.00

AC:

AN:

24116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17500

East Asian (EAS)

AF:

0.00

AC:

AN:

24352

South Asian (SAS)

AF:

0.00

AC:

AN:

47621

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29583

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3837

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

810646

Other (OTH)

AF:

0.00

AC:

AN:

43194

GnomAD4 genome

AF:

0.00000888

AC:

AN:

112593

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34773

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30524

American (AMR)

AF:

0.00

AC:

AN:

10837

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2657

East Asian (EAS)

AF:

0.00

AC:

AN:

3588

South Asian (SAS)

AF:

0.00

AC:

AN:

2845

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53359

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.0

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.061

T;T;T

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.

PhyloP100

-1.3

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.065

T;D;T

Sift4G

Benign

0.092

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.052

MutPred

0.43

Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);

MVP

0.11

MPC

0.27

ClinPred

0.086

GERP RS

-5.6

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.14

Mutation Taster

=98/2

polymorphism

(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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NM_001183.6:c.71C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over