chr17-38799337-A-G

Variant names:

• chr17-38799337-A-G
• NM_003559.5:c.88T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003559.5(PIP4K2B):​c.88T>C​(p.Cys30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIP4K2B NM_003559.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.982
• Publications: 0 publications found

Genes affected

PIP4K2B (HGNC:8998): (phosphatidylinositol-5-phosphate 4-kinase type 2 beta) The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. The encoded protein sequence does not show similarity to other kinases, but the protein does exhibit kinase activity. Additionally, the encoded protein interacts with p55 TNF receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055801958).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003559.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2B	NM_003559.5	MANE Select	c.88T>C	p.Cys30Arg	missense	Exon 1 of 10	NP_003550.1	P78356-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2B	ENST00000619039.5	TSL:1 MANE Select	c.88T>C	p.Cys30Arg	missense	Exon 1 of 10	ENSP00000482548.1	P78356-1
	PIP4K2B	ENST00000862415.1		c.88T>C	p.Cys30Arg	missense	Exon 1 of 10	ENSP00000532474.1
	PIP4K2B	ENST00000617499.1	TSL:4	c.-191+647T>C		intron	N/A	ENSP00000477549.1	A0A087WT35

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.81	N
PhyloP100		0.98
PrimateAI	Pathogenic	0.91	D
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.43		Gain of disorder (P = 0.0199)
MVP		0.043
ClinPred		0.90	D
GERP RS		1.6
PromoterAI		0.035	Neutral
Varity_R		0.45
gMVP		0.77

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

hg19: chr17-36955590;