X-154428763-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/19 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

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26
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-DT (HGNC:25138): (ATP6AP1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
ATP6AP1NM_001183.6 linkc.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
ATP6AP1ENST00000369762.7 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 10 1 NM_001183.6 ENSP00000358777.2 Q15904

Frequencies

GnomAD3 genomes
AF:
0.00000888
AC:
1
AN:
112593
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
34773
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:
0
AN:
1022305
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
330363
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000888
AC:
1
AN:
112593
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
34773
show subpopulations
Gnomad4 AFR
AF:
0.0000328
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
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
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
1.0
DANN
Benign
0.95
DEOGEN2
Benign
0.061
T;T;T
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.72
T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.084
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.
PrimateAI
Uncertain
0.67
T
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
T
GERP RS
-5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.030
gMVP
0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1432010564; hg19: chrX-153657109; API