chr14-20461276-C-T

Variant names:

• chr14-20461276-C-T
• rs1308457468
• NM_144568.4:c.50G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144568.4(PIP4P1):​c.50G>A​(p.Gly17Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIP4P1 NM_144568.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18849742).

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.50G>A	p.Gly17Asp	missense	Exon 1 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.50G>A	p.Gly17Asp	missense	Exon 1 of 7	NP_001094284.1	Q86T03-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4P1	ENST00000250489.9	TSL:1 MANE Select	c.50G>A	p.Gly17Asp	missense	Exon 1 of 7	ENSP00000250489.4	Q86T03-1
	PIP4P1	ENST00000398020.6	TSL:1	c.50G>A	p.Gly17Asp	missense	Exon 1 of 7	ENSP00000381102.4	Q86T03-2
	PIP4P1	ENST00000924695.1		c.50G>A	p.Gly17Asp	missense	Exon 1 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 65370 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1134806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 541646

African (AFR) AF: 0.00 AC: 0 AN: 24510

American (AMR) AF: 0.00 AC: 0 AN: 15690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14940

East Asian (EAS) AF: 0.00 AC: 0 AN: 29334

South Asian (SAS) AF: 0.00 AC: 0 AN: 23906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4394

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 946172

Other (OTH) AF: 0.00 AC: 0 AN: 45494

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.15
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.60	T
PhyloP100		4.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.47	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Sift4G	Benign	0.38	T
Polyphen		0.58	P
Vest4		0.21
MutPred		0.54		Gain of catalytic residue at A19 (P = 0)
MVP		0.19
MPC		1.7
ClinPred		0.93	D
GERP RS		3.8
PromoterAI		0.072	Neutral
Varity_R		0.30
gMVP		0.48
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1308457468; hg19: chr14-20929435;