22-20710853-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_058004.4(PI4KA):​c.5929G>A​(p.Gly1977Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PI4KA
NM_058004.4 missense

Scores

14
3
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.64
Variant links:
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PI4KANM_058004.4 linkc.5929G>A p.Gly1977Ser missense_variant Exon 52 of 55 ENST00000255882.11 NP_477352.3 P42356-1Q4LE69B4DYG5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PI4KAENST00000255882.11 linkc.5929G>A p.Gly1977Ser missense_variant Exon 52 of 55 1 NM_058004.4 ENSP00000255882.6 P42356-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 28, 2022The c.5929G>A (p.G1977S) alteration is located in exon 52 (coding exon 52) of the PI4KA gene. This alteration results from a G to A substitution at nucleotide position 5929, causing the glycine (G) at amino acid position 1977 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.87
D;.
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Pathogenic
0.53
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Pathogenic
0.90
D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-5.7
.;D
REVEL
Pathogenic
0.91
Sift
Uncertain
0.011
.;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
.;D
Vest4
0.92
MVP
0.95
MPC
2.6
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.59
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-21065141; API