Variant 15-43534939-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001394395.1(PPIP5K1):c.4208T>C(p.Val1403Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

PPIP5K1
NM_001394395.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.219

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024791181).

BP6

Variant 15-43534939-A-G is Benign according to our data. Variant chr15-43534939-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3217241.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K1	NM_001394395.1 linkuse as main transcript	c.4208T>C	p.Val1403Ala	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.4208T>C	p.Val1403Ala	missense_variant	32/32	5	NM_001394395.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251438

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.5

DANN

Benign

0.56

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.52

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

M_CAP

Benign

0.0019

MetaRNN

Benign

0.025

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

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.15

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

REVEL

Benign

0.032

Sift

Benign

0.36

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

Sift4G

Benign

0.34

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

Polyphen

0.0

B;.;B;B;B;B;B;.

Vest4

0.060

MutPred

0.33

.;.;Loss of stability (P = 0.0103);.;.;.;Loss of stability (P = 0.0103);.;

MVP

0.040

MPC

0.13

ClinPred

0.039

GERP RS

-0.67

Varity_R

0.027

gMVP

0.12

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

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