rs1555977799
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005765.3(ATP6AP2):c.408G>A(p.Met136Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,135 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Consequence
ATP6AP2
NM_005765.3 missense
NM_005765.3 missense
Scores
4
4
5
Clinical Significance
Conservation
PhyloP100: 9.27
Genes affected
ATP6AP2 (HGNC:18305): (ATPase H+ transporting accessory protein 2) This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6AP2 | NM_005765.3 | c.408G>A | p.Met136Ile | missense_variant | 5/9 | ENST00000636580.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6AP2 | ENST00000636580.2 | c.408G>A | p.Met136Ile | missense_variant | 5/9 | 1 | NM_005765.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097135Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1AN XY: 362533
GnomAD4 exome
AF:
AC:
2
AN:
1097135
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Cov.:
30
AF XY:
AC XY:
1
AN XY:
362533
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Syndromic X-linked intellectual disability Hedera type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 465129). This variant has not been reported in the literature in individuals affected with ATP6AP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 136 of the ATP6AP2 protein (p.Met136Ile). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T;T;.;T;.;T;.;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
REVEL
Benign
Polyphen
0.56, 0.73
.;P;.;P;.;.;.;.;.;.;.;.
Vest4
0.62
MutPred
0.38
.;Loss of ubiquitination at K139 (P = 0.0982);.;.;.;Loss of ubiquitination at K139 (P = 0.0982);Loss of ubiquitination at K139 (P = 0.0982);.;Loss of ubiquitination at K139 (P = 0.0982);.;.;Loss of ubiquitination at K139 (P = 0.0982);
MVP
MPC
0.72
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at