Variant 15-43535426-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394395.1(PPIP5K1):c.3721A>G(p.Thr1241Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,611,506 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PPIP5K1
NM_001394395.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

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]

PPIP5K1 links:

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ACMG classification

Classification made for transcript

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=0.14701772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K1	NM_001394395.1 linkuse as main transcript	c.3721A>G	p.Thr1241Ala	missense_variant	32/32	ENST00000420765.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K1	ENST00000420765.6 linkuse as main transcript	c.3721A>G	p.Thr1241Ala	missense_variant	32/32	5	NM_001394395.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1459472

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000605

Hom.:

Bravo

AF:

0.0000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 14, 2024

The c.3550A>G (p.T1184A) alteration is located in exon 31 (coding exon 29) of the PPIP5K1 gene. This alteration results from a A to G substitution at nucleotide position 3550, causing the threonine (T) at amino acid position 1184 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

Benign

0.077

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;.;T;.;.;.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.59

T;T;.;.;.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.81

.;.;L;.;.;.;L;.

MutationTaster

Benign

0.67

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N;N

REVEL

Benign

0.089

Sift

Uncertain

0.013

D;D;D;D;D;D;D;D

Sift4G

Benign

0.089

T;T;T;T;T;T;T;T

Polyphen

0.23

B;.;D;D;B;D;D;.

Vest4

0.14

MutPred

0.17

.;.;Loss of glycosylation at T1184 (P = 0.0031);.;.;.;Loss of glycosylation at T1184 (P = 0.0031);.;

MVP

0.33

MPC

0.36

ClinPred

0.85

GERP RS

4.6

Varity_R

0.085

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over