rs1078109

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024779.5. 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
	PIP4K2C	NM_024779.5	MANE Select	c.174+1120G>A		intron	N/A	NP_079055.3
	PIP4K2C	NM_001146258.2		c.174+1120G>A		intron	N/A	NP_001139730.1
	PIP4K2C	NM_001146259.2		c.174+1120G>A		intron	N/A	NP_001139731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2C	ENST00000354947.10	TSL:1 MANE Select	c.174+1120G>A		intron	N/A	ENSP00000347032.5
	PIP4K2C	ENST00000540759.6	TSL:2	c.174+1120G>A		intron	N/A	ENSP00000439878.2
	PIP4K2C	ENST00000550465.5	TSL:2	c.174+1120G>A		intron	N/A	ENSP00000447390.1

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

African (AFR) AF: 0.0168 AC: 696 AN: 41538

American (AMR) AF: 0.0455 AC: 696 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0416 AC: 200 AN: 4810

European-Finnish (FIN) AF: 0.0569 AC: 603 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6515 AN: 67984

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0644 Hom.: 269

Bravo AF: 0.0561

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		-1.0
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: rs1078109; hg19: chr12-57986366;