chr14-20461187-C-T

Variant names:

• chr14-20461187-C-T
• rs533921782
• NM_144568.4:c.139G>A

Variant summary

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

The NM_144568.4(PIP4P1):​c.139G>A​(p.Ala47Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000595 in 1,261,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: PIP4P1 NM_144568.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.877
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030651748).

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.139G>A	p.Ala47Thr	missense	Exon 1 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.139G>A	p.Ala47Thr	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.139G>A	p.Ala47Thr	missense	Exon 1 of 7	ENSP00000250489.4	Q86T03-1
	PIP4P1	ENST00000398020.6	TSL:1	c.139G>A	p.Ala47Thr	missense	Exon 1 of 7	ENSP00000381102.4	Q86T03-2
	PIP4P1	ENST00000924695.1		c.139G>A	p.Ala47Thr	missense	Exon 1 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.000559

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000229 AC: 3 AN: 13088 AF XY: 0.000289

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000842

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000783

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000635 AC: 704 AN: 1109214 Hom.: 0 Cov.: 31 AF XY: 0.000634 AC XY: 333 AN XY: 525172

African (AFR) AF: 0.00 AC: 0 AN: 23122

American (AMR) AF: 0.000191 AC: 2 AN: 10482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14602

East Asian (EAS) AF: 0.00 AC: 0 AN: 26748

South Asian (SAS) AF: 0.00 AC: 0 AN: 23290

European-Finnish (FIN) AF: 0.0000304 AC: 1 AN: 32894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3580

European-Non Finnish (NFE) AF: 0.000731 AC: 680 AN: 929842

Other (OTH) AF: 0.000470 AC: 21 AN: 44654

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74426

African (AFR) AF: 0.0000481 AC: 2 AN: 41556

American (AMR) AF: 0.000326 AC: 5 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 67948

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.000321

ExAC AF: 0.000213 AC: 19

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	0.079
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.88
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.065
Sift	Benign	0.13	T
Sift4G	Benign	0.54	T
Polyphen		0.013	B
Vest4		0.19
MVP		0.043
MPC		0.58
ClinPred		0.11	T
GERP RS		3.5
PromoterAI		0.10	Neutral
Varity_R		0.16
gMVP		0.15
Mutation Taster		=90/10	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: rs533921782; hg19: chr14-20929346;