rs121918521
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PP5_ModerateBP4BP7
The NM_005765.3(ATP6AP2):c.321C>T(p.Asp107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 24)
Consequence
ATP6AP2
NM_005765.3 synonymous
NM_005765.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.94
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;
PP5
?
Variant X-40597269-C-T is Pathogenic according to our data. Variant chrX-40597269-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 10801.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-40597269-C-T is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34). . Strength limited to SUPPORTING due to the PP5.
BP7
?
Synonymous conserved (PhyloP=1.94 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6AP2 | NM_005765.3 | c.321C>T | p.Asp107= | synonymous_variant | 4/9 | ENST00000636580.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6AP2 | ENST00000636580.2 | c.321C>T | p.Asp107= | synonymous_variant | 4/9 | 1 | NM_005765.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Syndromic X-linked intellectual disability Hedera type Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2022 | This variant has been observed in individual(s) with clinical features of ATP6AP2-related conditions (PMID: 15746149). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. Experimental studies have shown that this variant affects ATP6AP2 function (PMID: 15746149). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 10801). This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 107 of the ATP6AP2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATP6AP2 protein. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 15, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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