rs748826712

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018710.3(PIP4P2):​c.370A>T​(p.Ile124Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I124V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PIP4P2
NM_018710.3 missense

Scores

4
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.95
Variant links:
Genes affected
PIP4P2 (HGNC:25452): (phosphatidylinositol-4,5-bisphosphate 4-phosphatase 2) TMEM55A 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIP4P2NM_018710.3 linkc.370A>T p.Ile124Leu missense_variant Exon 4 of 7 ENST00000285419.8 NP_061180.1 Q8N4L2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIP4P2ENST00000285419.8 linkc.370A>T p.Ile124Leu missense_variant Exon 4 of 7 1 NM_018710.3 ENSP00000285419.3 Q8N4L2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461638
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727114
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.097
T;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.39
T
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.035
D;.
Polyphen
0.70
P;.
Vest4
0.66
MutPred
0.75
Loss of sheet (P = 0.1158);.;
MVP
0.46
MPC
0.87
ClinPred
0.90
D
GERP RS
5.7
Varity_R
0.52
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-92030734; API