NM_005028.5:c.145-27388A>G

Variant names:

• chr10-22637105-T-C
• rs1778329
• NM_005028.5:c.145-27388A>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.145-27388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,228 control chromosomes in the GnomAD database, including 973 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 0.085 (973 hom., cov: 32)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.145-27388A>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.145-27388A>G		intron_variant	Intron 1 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.-33-27388A>G		intron_variant	Intron 1 of 9	2		ENSP00000442098.1

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12818 AN: 152110 Hom.: 953 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0846 AC: 12877 AN: 152228 Hom.: 973 Cov.: 32 AF XY: 0.0835 AC XY: 6211 AN XY: 74420

African (AFR) AF: 0.204 AC: 8454 AN: 41508

American (AMR) AF: 0.0517 AC: 790 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0387 AC: 187 AN: 4826

European-Finnish (FIN) AF: 0.0312 AC: 331 AN: 10604

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2714 AN: 68016

Other (OTH) AF: 0.0747 AC: 158 AN: 2116

Alfa AF: 0.0634 Hom.: 201

Bravo AF: 0.0913

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.37
PhyloP100		-0.36
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: rs1778329; hg19: chr10-22926034;