Genetic Variant NM_144568.4:c.107G>A (chr14-20461219-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144568.4(PIP4P1):c.107G>A(p.Gly36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,255,902 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 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

PIP4P1
NM_144568.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Publications

0 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018783778).

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.107G>A	p.Gly36Glu	missense	Exon 1 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.107G>A	p.Gly36Glu	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.107G>A	p.Gly36Glu	missense	Exon 1 of 7	ENSP00000250489.4	Q86T03-1
PIP4P1	ENST00000398020.6	TSL:1	c.107G>A	p.Gly36Glu	missense	Exon 1 of 7	ENSP00000381102.4	Q86T03-2
PIP4P1	ENST00000924695.1		c.107G>A	p.Gly36Glu	missense	Exon 1 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000591

AC:

AN:

16930

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000453

AC:

AN:

1103824

Hom.:

Cov.:

AF XY:

0.00000191

AC XY:

AN XY:

522718

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

23342

American (AMR)

AF:

0.00

AC:

AN:

9826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14494

East Asian (EAS)

AF:

0.00

AC:

AN:

27032

South Asian (SAS)

AF:

0.00

AC:

AN:

21334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3936

European-Non Finnish (NFE)

AF:

0.00000216

AC:

AN:

927014

Other (OTH)

AF:

0.00

AC:

AN:

44326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

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:

0.0000592

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

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:

0.000106

ExAC

AF:

0.0000303

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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.78

M_CAP

Benign

0.0067

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

PhyloP100

2.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.16

REVEL

Benign

0.091

Sift

Uncertain

0.012

Sift4G

Benign

0.075

Polyphen

0.47

Vest4

0.32

MutPred

0.51

Gain of catalytic residue at A32 (P = 2e-04)

MVP

0.043

MPC

1.1

ClinPred

0.21

GERP RS

4.5

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.54

Mutation Taster

=67/33

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