10-22714297-A-G

Variant names:

• chr10-22714297-A-G
• rs1132816
• NM_005028.5:c.30T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005028.5(PIP4K2A):​c.30T>C​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,608,664 control chromosomes in the GnomAD database, including 62,365 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 0.32 (9306 hom., cov: 30)
  • Exomes 𝑓: 0.26 (53059 hom.)
• Consequence: PIP4K2A NM_005028.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 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.30T>C	p.Ser10Ser	synonymous	Exon 1 of 10	NP_005019.2
	PIP4K2A	NM_001330062.2		c.-395T>C		upstream_gene	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.30T>C	p.Ser10Ser	synonymous	Exon 1 of 10	ENSP00000365757.4
	PIP4K2A	ENST00000545335.5	TSL:2	c.-395T>C		upstream_gene	N/A	ENSP00000442098.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48556 AN: 151294 Hom.: 9283 Cov.: 30

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.247 AC: 60081 AN: 243608 AF XY: 0.247

Gnomad AFR exome AF: 0.559

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.262 AC: 381471 AN: 1457252 Hom.: 53059 Cov.: 33 AF XY: 0.261 AC XY: 189544 AN XY: 725108

African (AFR) AF: 0.556 AC: 18401 AN: 33092

American (AMR) AF: 0.143 AC: 6348 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 5055 AN: 25948

East Asian (EAS) AF: 0.0767 AC: 3003 AN: 39142

South Asian (SAS) AF: 0.283 AC: 24386 AN: 86044

European-Finnish (FIN) AF: 0.190 AC: 10109 AN: 53114

Middle Eastern (MID) AF: 0.290 AC: 1669 AN: 5758

European-Non Finnish (NFE) AF: 0.267 AC: 296432 AN: 1109572

Other (OTH) AF: 0.267 AC: 16068 AN: 60122

GnomAD4 genome AF: 0.321 AC: 48628 AN: 151412 Hom.: 9306 Cov.: 30 AF XY: 0.312 AC XY: 23095 AN XY: 74014

African (AFR) AF: 0.543 AC: 22436 AN: 41288

American (AMR) AF: 0.206 AC: 3150 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 646 AN: 3462

East Asian (EAS) AF: 0.102 AC: 523 AN: 5112

South Asian (SAS) AF: 0.275 AC: 1318 AN: 4798

European-Finnish (FIN) AF: 0.171 AC: 1790 AN: 10462

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.264 AC: 17869 AN: 67730

Other (OTH) AF: 0.294 AC: 618 AN: 2100

Alfa AF: 0.290 Hom.: 3692

Bravo AF: 0.333

Asia WGS AF: 0.221 AC: 770 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.61
PhyloP100		-1.5
PromoterAI		0.052	Neutral
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: rs1132816; hg19: chr10-23003226; COSMIC: COSV64862525; COSMIC: COSV64862525;