17-38799337-A-G

Position:

• chr17-38799337-A-G

Variant summary

Our verdict is Likely benign. Variant got -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. 11/18 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

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]

PIP4K2B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2B	NM_003559.5	c.88T>C	p.Cys30Arg	missense_variant	1/10	ENST00000619039.5	NP_003550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2B	ENST00000619039.5	c.88T>C	p.Cys30Arg	missense_variant	1/10	1	NM_003559.5	ENSP00000482548.1
PIP4K2B	ENST00000617499.1	c.-191+647T>C		intron_variant		4		ENSP00000477549.1
PIP4K2B	ENST00000617781.1	n.186T>C		non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.88T>C (p.C30R) alteration is located in exon 1 (coding exon 1) of the PIP4K2B gene. This alteration results from a T to C substitution at nucleotide position 88, causing the cysteine (C) at amino acid position 30 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-36955590;