rs1053454

chr10-22537164-A-Cchr10-22537164-A-Gchr10-22537164-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005028.5(PIP4K2A):c.*37T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,526,178 control chromosomes in the GnomAD database, including 326,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (38556 hom., cov: 29)
  • Exomes 𝑓: 0.64 (288201 hom.)
• Consequence: PIP4K2A NM_005028.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIP4K2A	NM_005028.5	c.*37T>G		3_prime_UTR_variant	10/10	ENST00000376573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.*37T>G		3_prime_UTR_variant	10/10	1	NM_005028.5	P1
PIP4K2A	ENST00000323883.11	c.*37T>G		3_prime_UTR_variant	8/8	2
PIP4K2A	ENST00000545335.5	c.*37T>G		3_prime_UTR_variant	10/10	2
PIP4K2A	ENST00000474335.1	n.288T>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107143 AN: 151612 Hom.: 38511 Cov.: 29

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.716

GnomAD3 exomes AF: 0.692 AC: 137999 AN: 199472 Hom.: 48413 AF XY: 0.690 AC XY: 73562 AN XY: 106626

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.825

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.770

Gnomad FIN exome AF: 0.635

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.644 AC: 885794 AN: 1374446 Hom.: 288201 Cov.: 20 AF XY: 0.647 AC XY: 442368 AN XY: 683738

Gnomad4 AFR exome AF: 0.835

Gnomad4 AMR exome AF: 0.817

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.707 AC: 107255 AN: 151732 Hom.: 38556 Cov.: 29 AF XY: 0.713 AC XY: 52807 AN XY: 74114

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.715

Alfa AF: 0.660 Hom.: 34482

Bravo AF: 0.716

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.4
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1053454; hg19: chr10-22826093; COSMIC: COSV60540594; COSMIC: COSV60540594;