chr15-43539529-G-A

Position:

• chr15-43539529-G-A

Variant summary

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

The NM_001394395.1(PPIP5K1):​c.3611C>T​(p.Pro1204Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIP5K1 NM_001394395.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.45

Genes affected

PPIP5K1 (HGNC:29023): (diphosphoinositol pentakisphosphate kinase 1) This gene encodes a dual functional inositol kinase. The encoded enzyme converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate and diphosphoinositol pentakisphosphate to bis-diphosphoinositol tetrakisphosphate. This protein may be important for intracellular signaling pathways. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 15.[provided by RefSeq, Jun 2010]

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=0.20898247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K1	NM_001394395.1	c.3611C>T	p.Pro1204Leu	missense_variant	31/32	ENST00000420765.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K1	ENST00000420765.6	c.3611C>T	p.Pro1204Leu	missense_variant	31/32	5	NM_001394395.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 02, 2021

The c.3440C>T (p.P1147L) alteration is located in exon 30 (coding exon 28) of the PPIP5K1 gene. This alteration results from a C to T substitution at nucleotide position 3440, causing the proline (P) at amino acid position 1147 to be replaced by a leucine (L). 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	0.098
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;.;.;.;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N;N;N;.
REVEL	Benign	0.080
Sift	Benign	0.61	T;D;D;D;T;D;D;D;.
Sift4G	Uncertain	0.040	D;T;T;T;D;T;T;T;.
Polyphen		0.89	P;.;P;P;P;P;P;.;.
Vest4		0.25
MutPred		0.13		.;.;Loss of catalytic residue at P1146 (P = 0.0116);.;.;.;Loss of catalytic residue at P1146 (P = 0.0116);.;.;
MVP		0.40
MPC		0.11
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-43831727;