Variant 1-56524400-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003713.5(PLPP3):c.452T>C(p.Ile151Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PLPP3
NM_003713.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

Variant links:

Genes affected

PLPP3 (HGNC:9229): (phospholipid phosphatase 3) The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid and short-chain phosphatidic acid. The expression of this gene is found to be enhanced by epidermal growth factor in Hela cells. [provided by RefSeq, Mar 2010]

PLPP3 links:

ENSG00000284686 (HGNC:):

ENSG00000284686 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5 linkuse as main transcript	c.452T>C	p.Ile151Thr	missense_variant	3/6	ENST00000371250.4	NP_003704.3	O14495

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLPP3	ENST00000371250.4 linkuse as main transcript	c.452T>C	p.Ile151Thr	missense_variant	3/6	1	NM_003713.5	ENSP00000360296.3	O14495
ENSG00000284686	ENST00000642129.1 linkuse as main transcript	n.95T>C		non_coding_transcript_exon_variant	1/6			ENSP00000492927.1	A0A286YES4
PLPP3	ENST00000461655.1 linkuse as main transcript	n.554T>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250842

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135524

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727192

show subpopulations

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:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.452T>C (p.I151T) alteration is located in exon 3 (coding exon 3) of the PLPP3 gene. This alteration results from a T to C substitution at nucleotide position 452, causing the isoleucine (I) at amino acid position 151 to be replaced by a threonine (T). 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

Benign

0.25

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

Eigen

Benign

0.088

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.60

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.53

Sift

Uncertain

0.019

Sift4G

Uncertain

0.012

Polyphen

0.15

Vest4

0.62

MutPred

0.81

Loss of stability (P = 0.0098);

MVP

0.58

MPC

0.77

ClinPred

0.75

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over