chr15-43534749-C-A

Position:

• chr15-43534749-C-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.4398G>T​(p.Glu1466Asp) 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: PPIP5K1 NM_001394395.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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=0.100138515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K1	NM_001394395.1	c.4398G>T	p.Glu1466Asp	missense_variant	32/32	ENST00000420765.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K1	ENST00000420765.6	c.4398G>T	p.Glu1466Asp	missense_variant	32/32	5	NM_001394395.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.87	D;D;.;.;.;D;D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.45	N;N;N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.034	D;T;T;D;D;D;T;T
Polyphen		0.99	D;.;P;P;D;P;P;.
Vest4		0.18
MutPred		0.15		.;.;Loss of disorder (P = 0.1508);.;.;.;Loss of disorder (P = 0.1508);.;
MVP		0.22
MPC		0.23
ClinPred		0.78	D
GERP RS		0.30
Varity_R		0.26
gMVP		0.065

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: chr15-43826947;