rs1078109

Variant names:

• chr12-57592583-G-A
• rs1078109
• NM_024779.5:c.174+1120G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024779.5(PIP4K2C):​c.174+1120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 152,188 control chromosomes in the GnomAD database, including 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 0.059 (365 hom., cov: 31)
• Consequence: PIP4K2C NM_024779.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

PIP4K2C (HGNC:23786): (phosphatidylinositol-5-phosphate 4-kinase type 2 gamma) Enables 1-phosphatidylinositol-4-phosphate 5-kinase activity and identical protein binding activity. Involved in several processes, including 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activity; and positive regulation of autophagosome assembly. Located in several cellular components, including autophagosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2C	NM_024779.5	c.174+1120G>A		intron_variant	Intron 1 of 9	ENST00000354947.10	NP_079055.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2C	ENST00000354947.10	c.174+1120G>A		intron_variant	Intron 1 of 9	1	NM_024779.5	ENSP00000347032.5

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9058 AN: 152070 Hom.: 366 Cov.: 31

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0595 AC: 9050 AN: 152188 Hom.: 365 Cov.: 31 AF XY: 0.0558 AC XY: 4155 AN XY: 74396

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0569

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0772 Hom.: 177

Bravo AF: 0.0561

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs1078109; hg19: chr12-57986366;