Genetic Variant PIP4P1:p.Ala32Thr (chr14-20461232-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144568.4(PIP4P1):c.94G>A(p.Ala32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,260,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PIP4P1
NM_144568.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.957

Publications

1 publications found

Variant links:

Genes affected

PIP4P1 (HGNC:19299): (phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1) TMEM55B catalyzes the degradation of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) by removing the 4-phosphate (Ungewickell et al., 2005 [PubMed 16365287]).[supplied by OMIM, Mar 2008]

PIP4P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1716434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144568.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4P1	NM_144568.4	MANE Select	c.94G>A	p.Ala32Thr	missense	Exon 1 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.94G>A	p.Ala32Thr	missense	Exon 1 of 7	NP_001094284.1	Q86T03-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIP4P1	ENST00000250489.9	TSL:1 MANE Select	c.94G>A	p.Ala32Thr	missense	Exon 1 of 7	ENSP00000250489.4	Q86T03-1
PIP4P1	ENST00000398020.6	TSL:1	c.94G>A	p.Ala32Thr	missense	Exon 1 of 7	ENSP00000381102.4	Q86T03-2
PIP4P1	ENST00000924695.1		c.94G>A	p.Ala32Thr	missense	Exon 1 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000838

AC:

AN:

23866

AF XY:

0.00

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 FIN exome

AF:

0.000145

Gnomad NFE exome

AF:

0.0000966

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000205

AC:

227

AN:

1108818

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

106

AN XY:

525842

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23572

American (AMR)

AF:

0.00

AC:

AN:

10636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14552

East Asian (EAS)

AF:

0.00

AC:

AN:

27422

South Asian (SAS)

AF:

0.00

AC:

AN:

21632

European-Finnish (FIN)

AF:

0.0000618

AC:

AN:

32370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.000232

AC:

216

AN:

930068

Other (OTH)

AF:

0.000202

AC:

AN:

44458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67992

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000135

AC:

ExAC

AF:

0.0000689

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.61

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.97

PhyloP100

0.96

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.090

REVEL

Benign

0.090

Sift

Benign

0.34

Sift4G

Benign

0.70

Polyphen

0.99

Vest4

0.13

MVP

0.068

MPC

0.56

ClinPred

0.22

GERP RS

3.6

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.21

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over