rs1053454

Variant names:

• chr10-22537164-A-C
• rs1053454
• NM_005028.5:c.*37T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-22537164-A-C
• chr10-22537164-A-G
• chr10-22537164-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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: Benign. The variant received -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.

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.*37T>G		3_prime_UTR	Exon 10 of 10	NP_005019.2
	PIP4K2A	NM_001330062.2		c.*37T>G		3_prime_UTR	Exon 10 of 10	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.*37T>G		3_prime_UTR	Exon 10 of 10	ENSP00000365757.4	P48426-1
	PIP4K2A	ENST00000899822.1		c.*37T>G		3_prime_UTR	Exon 9 of 9	ENSP00000569881.1
	PIP4K2A	ENST00000545335.5	TSL:2	c.*37T>G		3_prime_UTR	Exon 10 of 10	ENSP00000442098.1	P48426-2

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

GnomAD2 exomes AF: 0.692 AC: 137999 AN: 199472 AF XY: 0.690

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 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

African (AFR) AF: 0.835 AC: 26185 AN: 31350

American (AMR) AF: 0.817 AC: 33451 AN: 40920

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 14929 AN: 25146

East Asian (EAS) AF: 0.632 AC: 23845 AN: 37736

South Asian (SAS) AF: 0.769 AC: 61970 AN: 80624

European-Finnish (FIN) AF: 0.632 AC: 32383 AN: 51268

Middle Eastern (MID) AF: 0.767 AC: 4305 AN: 5612

European-Non Finnish (NFE) AF: 0.623 AC: 651209 AN: 1044522

Other (OTH) AF: 0.655 AC: 37517 AN: 57268

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

African (AFR) AF: 0.831 AC: 34383 AN: 41384

American (AMR) AF: 0.778 AC: 11886 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2050 AN: 3468

East Asian (EAS) AF: 0.632 AC: 3257 AN: 5156

South Asian (SAS) AF: 0.779 AC: 3725 AN: 4784

European-Finnish (FIN) AF: 0.642 AC: 6726 AN: 10476

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43133 AN: 67894

Other (OTH) AF: 0.715 AC: 1504 AN: 2104

Alfa AF: 0.669 Hom.: 46145

Bravo AF: 0.716

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.54
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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