22-20710847-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PP2PP3BP4
The NM_058004.4(PI4KA):c.5935A>G(p.Met1979Val) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PI4KA
NM_058004.4 missense
NM_058004.4 missense
Scores
6
8
2
Clinical Significance
Conservation
PhyloP100: 7.75
Genes affected
PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a domain PI3K/PI4K catalytic (size 278) in uniprot entity PI4KA_HUMAN there are 7 pathogenic changes around while only 3 benign (70%) in NM_058004.4
PP2
?
Missense variant where missense usually causes diseases, PI4KA
PP3
?
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, phyloP100way_vertebrate, PrimateAI, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27490807).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PI4KA | NM_058004.4 | c.5935A>G | p.Met1979Val | missense_variant | 52/55 | ENST00000255882.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PI4KA | ENST00000255882.11 | c.5935A>G | p.Met1979Val | missense_variant | 52/55 | 1 | NM_058004.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 151916Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 genomes
?
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1
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33
FAILED QC
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GnomAD3 exomes AF: 0.000164 AC: 41AN: 250312Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135510
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000397 AC: 58AN: 1459778Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 726214
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 151916Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74178
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?
Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | PI4KA: PP2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
REVEL
Pathogenic
Sift4G
Uncertain
D;T
Polyphen
0.28
.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at