9-68889048-T-C

Variant summary

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

The NM_003558.4(PIP5K1B):c.386T>C(p.Val129Ala) 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: 7.92

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.386T>C	p.Val129Ala	missense_variant	7/16	ENST00000265382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP5K1B	ENST00000265382.8	c.386T>C	p.Val129Ala	missense_variant	7/16	1	NM_003558.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Oct 14, 2023

The c.386T>C (p.V129A) alteration is located in exon 7 (coding exon 4) of the PIP5K1B gene. This alteration results from a T to C substitution at nucleotide position 386, causing the valine (V) at amino acid position 129 to be replaced by an alanine (A). 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	0.85
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.8	M;M;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.055	T;T;D;D
Polyphen		0.46	.;P;.;.
Vest4		0.50
MutPred		0.66		Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);
MVP		0.76
MPC		1.7
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.48

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: chr9-71503964;