dbSNP rs773019722: PIP4P1:p.Gly36Ala (chr14-20461219-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144568.4(PIP4P1):c.107G>C(p.Gly36Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,256,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PIP4P1
NM_144568.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07430971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4P1	NM_144568.4 link	c.107G>C	p.Gly36Ala	missense_variant	Exon 1 of 7	ENST00000250489.9	NP_653169.2	Q86T03-1
PIP4P1	NM_001100814.3 link	c.107G>C	p.Gly36Ala	missense_variant	Exon 1 of 7		NP_001094284.1	Q86T03-2
PIP4P1	XM_024449739.2 link	c.107G>C	p.Gly36Ala	missense_variant	Exon 1 of 6		XP_024305507.1
PIP4P1	XM_024449740.2 link	c.107G>C	p.Gly36Ala	missense_variant	Exon 1 of 6		XP_024305508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIP4P1	ENST00000250489.9 link	c.107G>C	p.Gly36Ala	missense_variant	Exon 1 of 7	1	NM_144568.4	ENSP00000250489.4	Q86T03-1
PIP4P1	ENST00000398020.6 link	c.107G>C	p.Gly36Ala	missense_variant	Exon 1 of 7	1		ENSP00000381102.4	Q86T03-2
PIP4P1	ENST00000557041.1 link	n.183G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152078

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:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000354

AC:

AN:

16930

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

9152

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:

0.000718

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00526

GnomAD4 exome

AF:

0.0000272

AC:

AN:

1103824

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

522718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000892

Gnomad4 NFE exome

AF:

0.00000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

0.0011

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.019

D;T

Sift4G

Benign

0.071

T;T

Polyphen

0.27

B;P

Vest4

0.26

MVP

0.043

MPC

0.63

ClinPred

0.16

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over