10-22549460-A-C

Variant names:

• chr10-22549460-A-C
• rs10828316
• NM_005028.5:c.792+1199T>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.792+1199T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,072 control chromosomes in the GnomAD database, including 5,178 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 0.24 (5178 hom., cov: 30)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	NM_005028.5	MANE Select	c.792+1199T>G		intron	N/A	NP_005019.2
	PIP4K2A	NM_001330062.2		c.615+1199T>G		intron	N/A	NP_001316991.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	ENST00000376573.9	TSL:1 MANE Select	c.792+1199T>G		intron	N/A	ENSP00000365757.4
	PIP4K2A	ENST00000545335.5	TSL:2	c.615+1199T>G		intron	N/A	ENSP00000442098.1
	PIP4K2A	ENST00000323883.11	TSL:2	c.372+1199T>G		intron	N/A	ENSP00000326294.7

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36175 AN: 151956 Hom.: 5186 Cov.: 30

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.238 AC: 36171 AN: 152072 Hom.: 5178 Cov.: 30 AF XY: 0.234 AC XY: 17367 AN XY: 74312

African (AFR) AF: 0.0955 AC: 3967 AN: 41524

American (AMR) AF: 0.171 AC: 2607 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2105 AN: 5170

South Asian (SAS) AF: 0.199 AC: 960 AN: 4830

European-Finnish (FIN) AF: 0.308 AC: 3242 AN: 10526

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21132 AN: 67958

Other (OTH) AF: 0.229 AC: 483 AN: 2106

Alfa AF: 0.290 Hom.: 3554

Bravo AF: 0.227

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.54
PhyloP100		1.7
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: rs10828316; hg19: chr10-22838389;