rs777006911
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_058004.4(PI4KA):c.2386C>T(p.Arg796Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000559 in 1,611,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
PI4KA
NM_058004.4 stop_gained
NM_058004.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.18
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 Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-20765636-G-A is Pathogenic according to our data. Variant chr22-20765636-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 208450.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PI4KA | NM_058004.4 | c.2386C>T | p.Arg796Ter | stop_gained | 20/55 | ENST00000255882.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PI4KA | ENST00000255882.11 | c.2386C>T | p.Arg796Ter | stop_gained | 20/55 | 1 | NM_058004.4 | P1 | |
PI4KA | ENST00000466162.5 | n.149C>T | non_coding_transcript_exon_variant | 3/7 | 4 | ||||
PI4KA | ENST00000484220.1 | n.122C>T | non_coding_transcript_exon_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251444Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135900
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459292Hom.: 0 Cov.: 30 AF XY: 0.00000689 AC XY: 5AN XY: 725400
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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