Genetic Variant PIP4P1:p.Arg239Gln (chr14-20458677-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144568.4(PIP4P1):c.716G>A(p.Arg239Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PIP4P1
NM_144568.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.896

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052113563).

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.716G>A	p.Arg239Gln	missense	Exon 7 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.737G>A	p.Arg246Gln	missense	Exon 7 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.716G>A	p.Arg239Gln	missense	Exon 7 of 7	ENSP00000250489.4	Q86T03-1
PIP4P1	ENST00000398020.6	TSL:1	c.737G>A	p.Arg246Gln	missense	Exon 7 of 7	ENSP00000381102.4	Q86T03-2
PIP4P1	ENST00000924695.1		c.728G>A	p.Arg243Gln	missense	Exon 7 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

248624

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461050

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.0000450

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000900

AC:

AN:

1111712

Other (OTH)

AF:

0.0000166

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.063

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.033

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.78

M_CAP

Benign

0.0028

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

PhyloP100

-0.90

PrimateAI

Benign

0.26

PROVEAN

Benign

0.20

REVEL

Benign

0.091

Sift

Benign

0.54

Sift4G

Benign

0.67

Polyphen

0.0010

Vest4

0.059

MutPred

0.50

Gain of catalytic residue at Y240 (P = 0)

MVP

0.043

MPC

0.66

ClinPred

0.067

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

gMVP

0.33

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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