chr10-22607998-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005028.5(PIP4K2A):āc.268T>Gā(p.Phe90Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
PIP4K2A
NM_005028.5 missense
NM_005028.5 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIP4K2A | NM_005028.5 | c.268T>G | p.Phe90Val | missense_variant | 3/10 | ENST00000376573.9 | NP_005019.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIP4K2A | ENST00000376573.9 | c.268T>G | p.Phe90Val | missense_variant | 3/10 | 1 | NM_005028.5 | ENSP00000365757 | P1 | |
PIP4K2A | ENST00000545335.5 | c.91T>G | p.Phe31Val | missense_variant | 3/10 | 2 | ENSP00000442098 | |||
PIP4K2A | ENST00000422321.5 | n.124T>G | non_coding_transcript_exon_variant | 2/6 | 3 | |||||
PIP4K2A | ENST00000432610.1 | n.124T>G | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459790Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726282
GnomAD4 exome
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1
AN:
1459790
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Cov.:
29
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AC XY:
1
AN XY:
726282
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.268T>G (p.F90V) alteration is located in exon 3 (coding exon 3) of the PIP4K2A gene. This alteration results from a T to G substitution at nucleotide position 268, causing the phenylalanine (F) at amino acid position 90 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of stability (P = 0.078);.;
MVP
MPC
ClinPred
D
GERP RS
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
Publications
No publications associated with this variant yet.