Variant chr5-103154707-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001276277.3(PPIP5K2):c.1255T>G(p.Ser419Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00978 in 1,579,160 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 32)

Exomes 𝑓: 0.010 ( 99 hom. )

Consequence

PPIP5K2
NM_001276277.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

PPIP5K2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PPIP5K2. . Gene score misZ 3.8022 (greater than the threshold 3.09). Trascript score misZ 4.0872 (greater than threshold 3.09). GenCC has associacion of gene with hearing loss, autosomal recessive 100, hearing loss, autosomal recessive.

BP4

Computational evidence support a benign effect (MetaRNN=0.005351007).

BP6

Variant 5-103154707-T-G is Benign according to our data. Variant chr5-103154707-T-G is described in ClinVar as [Benign]. Clinvar id is 2655626.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIP5K2	NM_001276277.3 linkuse as main transcript	c.1255T>G	p.Ser419Ala	missense_variant	12/31	ENST00000358359.8	NP_001263206.1	O43314-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIP5K2	ENST00000358359.8 linkuse as main transcript	c.1255T>G	p.Ser419Ala	missense_variant	12/31	1	NM_001276277.3	ENSP00000351126.3		O43314-1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

991

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00681

AC:

1638

AN:

240504

Hom.:

AF XY:

0.00663

AC XY:

861

AN XY:

129902

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00395

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.00466

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00515

GnomAD4 exome

AF:

0.0101

AC:

14450

AN:

1426976

Hom.:

Cov.:

AF XY:

0.00987

AC XY:

7008

AN XY:

709974

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00443

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000643

Gnomad4 FIN exome

AF:

0.00601

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00725

GnomAD4 genome

AF:

0.00651

AC:

991

AN:

152184

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

423

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00415

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.00614

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.0116

AC:

ExAC

AF:

0.00761

AC:

923

Asia WGS

AF:

0.000290

AC:

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PPIP5K2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

PPIP5K2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Benign

0.87

DEOGEN2

Benign

0.011

.;.;T;T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

.;T;T;.;T;T

MetaRNN

Benign

0.0054

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;L;.;L;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.83

N;N;N;.;N;.

REVEL

Benign

0.027

Sift

Benign

0.78

T;T;T;.;T;.

Sift4G

Benign

0.76

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;B;.

Vest4

0.31

MVP

0.11

MPC

0.74

ClinPred

0.0097

GERP RS

3.4

Varity_R

0.050

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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