14-20461276-C-G

Variant names:

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

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>C​(p.Gly17Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. G17D) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PIP4P1 NM_144568.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.1447413).

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>C	p.Gly17Ala	missense	Exon 1 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.50G>C	p.Gly17Ala	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>C	p.Gly17Ala	missense	Exon 1 of 7	ENSP00000250489.4	Q86T03-1
	PIP4P1	ENST00000398020.6	TSL:1	c.50G>C	p.Gly17Ala	missense	Exon 1 of 7	ENSP00000381102.4	Q86T03-2
	PIP4P1	ENST00000924695.1		c.50G>C	p.Gly17Ala	missense	Exon 1 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.59	T
PhyloP100		4.4
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.10
Sift	Benign	0.18	T
Sift4G	Benign	0.70	T
Polyphen		0.076	B
Vest4		0.20
MutPred		0.55		Gain of catalytic residue at A19 (P = 0)
MVP		0.18
MPC		1.1
ClinPred		0.85	D
GERP RS		3.8
PromoterAI		-0.025	Neutral
Varity_R		0.19
gMVP		0.43
Mutation Taster		=76/24	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: rs1308457468; hg19: chr14-20929435;