9-68917672-T-C

Position:

• chr9-68917672-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003558.4(PIP5K1B):​c.896T>C​(p.Met299Thr) 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. 14/21 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: PIP5K1B NM_003558.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08149755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP5K1B	NM_003558.4	c.896T>C	p.Met299Thr	missense_variant	9/16	ENST00000265382.8	NP_003549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP5K1B	ENST00000265382.8	c.896T>C	p.Met299Thr	missense_variant	9/16	1	NM_003558.4	ENSP00000265382	P1
PIP5K1B	ENST00000478500.3	c.1016T>C	p.Met339Thr	missense_variant, NMD_transcript_variant	10/21	1		ENSP00000435778
PIP5K1B	ENST00000541509.5	c.896T>C	p.Met299Thr	missense_variant	8/14	2		ENSP00000438082

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

Feb 17, 2024

The c.896T>C (p.M299T) alteration is located in exon 9 (coding exon 6) of the PIP5K1B gene. This alteration results from a T to C substitution at nucleotide position 896, causing the methionine (M) at amino acid position 299 to be replaced by a threonine (T). 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	Benign	0.085
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.020	.;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.10	N;N
MutationTaster	Benign	0.79	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.082
Sift	Benign	0.58	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.0	.;B
Vest4		0.16
MutPred		0.51		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.32
MPC		1.1
ClinPred		0.10	T
GERP RS		-0.56
Varity_R		0.060
gMVP		0.55

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: chr9-71532588;