17-38780496-C-T

Variant names:

• chr17-38780496-C-T
• NM_003559.5:c.463G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003559.5(PIP4K2B):​c.463G>A​(p.Glu155Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.57

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2B	NM_003559.5	c.463G>A	p.Glu155Lys	missense_variant	Exon 4 of 10	ENST00000619039.5	NP_003550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2B	ENST00000619039.5	c.463G>A	p.Glu155Lys	missense_variant	Exon 4 of 10	1	NM_003559.5	ENSP00000482548.1
PIP4K2B	ENST00000617781.1	n.561G>A		non_coding_transcript_exon_variant	Exon 4 of 8	2
PIP4K2B	ENST00000617499.1	c.*57G>A		downstream_gene_variant		4		ENSP00000477549.1

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

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463G>A (p.E155K) alteration is located in exon 4 (coding exon 4) of the PIP4K2B gene. This alteration results from a G to A substitution at nucleotide position 463, causing the glutamic acid (E) at amino acid position 155 to be replaced by a lysine (K). 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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.56		Gain of MoRF binding (P = 0.0264);
MVP		0.23
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.73

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: chr17-36936749;