10-22591758-GGG-CGT

Variant names:

• chr10-22591758-GGG-CGT
• NM_005028.5:c.361_363delCCCinsACG
• PIP4K2A p.Pro121Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005028.5(PIP4K2A):​c.361_363delCCCinsACG​(p.Pro121Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P121S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIP4K2A NM_005028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005028.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	NM_005028.5	MANE Select	c.361_363delCCCinsACG	p.Pro121Thr	missense	N/A	NP_005019.2
	PIP4K2A	NM_001330062.2		c.184_186delCCCinsACG	p.Pro62Thr	missense	N/A	NP_001316991.1	P48426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	ENST00000376573.9	TSL:1 MANE Select	c.361_363delCCCinsACG	p.Pro121Thr	missense	N/A	ENSP00000365757.4	P48426-1
	PIP4K2A	ENST00000545335.5	TSL:2	c.184_186delCCCinsACG	p.Pro62Thr	missense	N/A	ENSP00000442098.1	P48426-2
	PIP4K2A	ENST00000928212.1		c.361_363delCCCinsACG	p.Pro121Thr	missense	N/A	ENSP00000598271.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-22880687;