Genetic Variant PLPPR3:p.Arg682Pro (chr19-812682-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001270366.2(PLPPR3):c.2045G>C(p.Arg682Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000801 in 1,048,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

PLPPR3
NM_001270366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

PLPPR3 (HGNC:23497): (phospholipid phosphatase related 3) The proteins in the lipid phosphate phosphatase (LPP) family, including PRG2, are integral membrane proteins that modulate bioactive lipid phosphates including phosphatidate, lysophosphatidate, and sphingosine-1-phosphate in the context of cell migration, neurite retraction, and mitogenesis (Brauer et al., 2003 [PubMed 12730698]).[supplied by OMIM, Mar 2008]

PLPPR3 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
PLPPR3	NM_001270366.2 link	c.2045G>C	p.Arg682Pro	missense_variant	Exon 8 of 8	ENST00000520876.8	NP_001257295.1	Q6T4P5-1
PLPPR3	NM_024888.3 link	c.2129G>C	p.Arg710Pro	missense_variant	Exon 7 of 7		NP_079164.1	Q6T4P5-3
PLPPR3	XM_011528317.4 link	c.2129G>C	p.Arg710Pro	missense_variant	Exon 7 of 7		XP_011526619.1	Q6T4P5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPPR3	ENST00000520876.8 link	c.2045G>C	p.Arg682Pro	missense_variant	Exon 8 of 8	1	NM_001270366.2	ENSP00000430297.1		Q6T4P5-1
PLPPR3	ENST00000359894.6 link	c.2129G>C	p.Arg710Pro	missense_variant	Exon 7 of 7	1		ENSP00000352962.2		Q6T4P5-3

Frequencies

GnomAD3 genomes

AF:

0.000123

AC:

AN:

146598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000678

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000355

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000455

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000731

AC:

AN:

902258

Hom.:

Cov.:

AF XY:

0.0000851

AC XY:

AN XY:

422958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000742

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000991

Gnomad4 NFE exome

AF:

0.0000734

Gnomad4 OTH exome

AF:

0.0000969

GnomAD4 genome

AF:

0.000123

AC:

AN:

146598

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

71282

show subpopulations

Gnomad4 AFR

AF:

0.0000489

Gnomad4 AMR

AF:

0.000678

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000355

Gnomad4 NFE

AF:

0.0000455

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000219

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2129G>C (p.R710P) alteration is located in exon 7 (coding exon 6) of the PLPPR3 gene. This alteration results from a G to C substitution at nucleotide position 2129, causing the arginine (R) at amino acid position 710 to be replaced by a proline (P). 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

0.29

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.43

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.81

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

1.0

D;D

Vest4

0.56

MutPred

0.27

.;Gain of glycosylation at R682 (P = 0.0236);

MVP

0.56

MPC

1.5

ClinPred

0.98

GERP RS

4.6

Varity_R

0.70

gMVP

0.40

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