rs764296974

Variant names:

• chr14-20459270-C-A
• NM_144568.4:c.626G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-20459270-C-A
• chr14-20459270-C-G
• chr14-20459270-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_144568.4(PIP4P1):​c.626G>T​(p.Arg209Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PIP4P1 NM_144568.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.86

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4P1	NM_144568.4	c.626G>T	p.Arg209Leu	missense_variant	Exon 6 of 7	ENST00000250489.9	NP_653169.2
PIP4P1	NM_001100814.3	c.647G>T	p.Arg216Leu	missense_variant	Exon 6 of 7		NP_001094284.1
PIP4P1	XM_024449739.2	c.541G>T	p.Val181Leu	missense_variant	Exon 5 of 6		XP_024305507.1
PIP4P1	XM_024449740.2	c.520G>T	p.Val174Leu	missense_variant	Exon 5 of 6		XP_024305508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4P1	ENST00000250489.9	c.626G>T	p.Arg209Leu	missense_variant	Exon 6 of 7	1	NM_144568.4	ENSP00000250489.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727244

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: 0.00000360

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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.047	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.078	T;T
Polyphen		1.0	D;D
Vest4		0.90
MutPred		0.69		Gain of catalytic residue at P208 (P = 0.0012);.;
MVP		0.56
MPC		1.7
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-20927429;