NM_018710.3:c.98G>A

Variant names:

• chr8-91040652-C-T
• rs1812293012
• NM_018710.3:c.98G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_018710.3(PIP4P2):​c.98G>A​(p.Ser33Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PIP4P2 NM_018710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25
• Publications: 0 publications found

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]

ENSG00000308751 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity PP4P2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1722641).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018710.3. 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
	PIP4P2	NM_018710.3	MANE Select	c.98G>A	p.Ser33Asn	missense	Exon 1 of 7	NP_061180.1	Q8N4L2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4P2	ENST00000285419.8	TSL:1 MANE Select	c.98G>A	p.Ser33Asn	missense	Exon 1 of 7	ENSP00000285419.3	Q8N4L2
	PIP4P2	ENST00000886895.1		c.98G>A	p.Ser33Asn	missense	Exon 1 of 8	ENSP00000556954.1
	PIP4P2	ENST00000886896.1		c.98G>A	p.Ser33Asn	missense	Exon 1 of 8	ENSP00000556955.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.087
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		5.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.037
Sift	Benign	0.36	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.34		Loss of glycosylation at S33 (P = 0.0025)
MVP		0.39
MPC		0.28
ClinPred		0.67	D
GERP RS		5.5
PromoterAI		0.0082	Neutral
Varity_R		0.37
gMVP		0.21
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs1812293012; hg19: chr8-92052880;