9-68919513-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003558.4(PIP5K1B):c.1018G>A(p.Glu340Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIP5K1B NM_003558.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.89

Genes affected

PIP5K1B (HGNC:8995): (phosphatidylinositol-4-phosphate 5-kinase type 1 beta) Predicted to enable 1-phosphatidylinositol-4-phosphate 5-kinase activity. Predicted to be involved in regulation of phosphatidylinositol 3-kinase signaling. Predicted to act upstream of or within phosphatidylinositol biosynthetic process. Located in uropod. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIP5K1B	NM_003558.4	c.1018G>A	p.Glu340Lys	missense_variant	10/16	ENST00000265382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP5K1B	ENST00000265382.8	c.1018G>A	p.Glu340Lys	missense_variant	10/16	1	NM_003558.4	P1
PIP5K1B	ENST00000478500.3	c.1138G>A	p.Glu380Lys	missense_variant, NMD_transcript_variant	11/21	1
PIP5K1B	ENST00000541509.5	c.1018G>A	p.Glu340Lys	missense_variant	9/14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

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

Nov 09, 2023

The c.1018G>A (p.E340K) alteration is located in exon 10 (coding exon 7) of the PIP5K1B gene. This alteration results from a G to A substitution at nucleotide position 1018, causing the glutamic acid (E) at amino acid position 340 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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Pathogenic	31
Dann	Uncertain	1.0
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	.;D
Vest4		0.58
MutPred		0.54		Gain of MoRF binding (P = 0.0079);Gain of MoRF binding (P = 0.0079);
MVP		0.90
MPC		2.2
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.83
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr9-71534429;