10-22536204-T-C

Variant names:

• chr10-22536204-T-C
• rs8341
• NM_005028.5:c.*997A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005028.5(PIP4K2A):​c.*997A>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 0.678 in 398,010 control chromosomes in the GnomAD database, including 92,630 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 (39226 hom., cov: 32)
  • Exomes 𝑓: 0.66 (53404 hom.)
• Consequence: PIP4K2A NM_005028.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 19 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.*997A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.*997A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_005028.5	ENSP00000365757.4

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108245 AN: 151996 Hom.: 39180 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.656 AC: 161426 AN: 245894 Hom.: 53404 Cov.: 0 AF XY: 0.655 AC XY: 81613 AN XY: 124574

African (AFR) AF: 0.828 AC: 5938 AN: 7174

American (AMR) AF: 0.796 AC: 5911 AN: 7428

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 5549 AN: 9228

East Asian (EAS) AF: 0.654 AC: 14940 AN: 22852

South Asian (SAS) AF: 0.771 AC: 2271 AN: 2944

European-Finnish (FIN) AF: 0.632 AC: 13155 AN: 20802

Middle Eastern (MID) AF: 0.756 AC: 978 AN: 1294

European-Non Finnish (NFE) AF: 0.644 AC: 101654 AN: 157826

Other (OTH) AF: 0.675 AC: 11030 AN: 16346

GnomAD4 genome AF: 0.712 AC: 108357 AN: 152116 Hom.: 39226 Cov.: 32 AF XY: 0.718 AC XY: 53366 AN XY: 74342

African (AFR) AF: 0.836 AC: 34709 AN: 41512

American (AMR) AF: 0.785 AC: 12004 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3359 AN: 5166

South Asian (SAS) AF: 0.778 AC: 3750 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6806 AN: 10550

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43536 AN: 67988

Other (OTH) AF: 0.723 AC: 1528 AN: 2114

Alfa AF: 0.677 Hom.: 13328

Bravo AF: 0.722

Asia WGS AF: 0.727 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.087
DANN	Benign	0.61
PhyloP100		-0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs8341; hg19: chr10-22825133;