14-20459265-T-C

Variant names:

• chr14-20459265-T-C
• NM_144568.4:c.631A>G

Variant summary

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

The NM_144568.4(PIP4P1):​c.631A>G​(p.Arg211Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIP4P1 NM_144568.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4P1	NM_144568.4	c.631A>G	p.Arg211Gly	missense_variant	Exon 6 of 7	ENST00000250489.9	NP_653169.2
PIP4P1	NM_001100814.3	c.652A>G	p.Arg218Gly	missense_variant	Exon 6 of 7		NP_001094284.1
PIP4P1	XM_024449739.2	c.546A>G	p.Arg182Arg	synonymous_variant	Exon 5 of 6		XP_024305507.1
PIP4P1	XM_024449740.2	c.525A>G	p.Arg175Arg	synonymous_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.631A>G	p.Arg211Gly	missense_variant	Exon 6 of 7	1	NM_144568.4	ENSP00000250489.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.652A>G (p.R218G) alteration is located in exon 6 (coding exon 6) of the TMEM55B gene. This alteration results from a A to G substitution at nucleotide position 652, causing the arginine (R) at amino acid position 218 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	-0.074	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.93
MutPred		0.73		Gain of catalytic residue at P208 (P = 0.0012);.;
MVP		0.73
MPC		1.5
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.87
gMVP		0.92

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: chr14-20927424;