10-22643562-T-C

Variant names:

• chr10-22643562-T-C
• rs1409395
• NM_005028.5:c.145-33845A>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.145-33845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,994 control chromosomes in the GnomAD database, including 5,152 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 0.25 (5152 hom., cov: 31)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 2 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.145-33845A>G		intron_variant	Intron 1 of 9	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.145-33845A>G		intron_variant	Intron 1 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.-33-33845A>G		intron_variant	Intron 1 of 9	2		ENSP00000442098.1
PIP4K2A	ENST00000605011.1	n.518-1500A>G		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37968 AN: 151876 Hom.: 5140 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.250 AC: 38013 AN: 151994 Hom.: 5152 Cov.: 31 AF XY: 0.246 AC XY: 18282 AN XY: 74284

African (AFR) AF: 0.194 AC: 8035 AN: 41448

American (AMR) AF: 0.175 AC: 2679 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3468

East Asian (EAS) AF: 0.0303 AC: 157 AN: 5176

South Asian (SAS) AF: 0.276 AC: 1328 AN: 4812

European-Finnish (FIN) AF: 0.276 AC: 2905 AN: 10542

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20893 AN: 67962

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.284 Hom.: 23756

Bravo AF: 0.239

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.64
DANN	Benign	0.76
PhyloP100		-0.32
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: rs1409395; hg19: chr10-22932491;