19-812682-C-G

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

3
9
6

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]

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
PLPPR3NM_001270366.2 linkc.2045G>C p.Arg682Pro missense_variant Exon 8 of 8 ENST00000520876.8 NP_001257295.1 Q6T4P5-1
PLPPR3NM_024888.3 linkc.2129G>C p.Arg710Pro missense_variant Exon 7 of 7 NP_079164.1 Q6T4P5-3
PLPPR3XM_011528317.4 linkc.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
PLPPR3ENST00000520876.8 linkc.2045G>C p.Arg682Pro missense_variant Exon 8 of 8 1 NM_001270366.2 ENSP00000430297.1 Q6T4P5-1
PLPPR3ENST00000359894.6 linkc.2129G>C p.Arg710Pro missense_variant Exon 7 of 7 1 ENSP00000352962.2 Q6T4P5-3

Frequencies

GnomAD3 genomes
AF:
0.000123
AC:
18
AN:
146598
Hom.:
0
Cov.:
32
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:
66
AN:
902258
Hom.:
0
Cov.:
34
AF XY:
0.0000851
AC XY:
36
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:
18
AN:
146598
Hom.:
0
Cov.:
32
AF XY:
0.000196
AC XY:
14
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.:
0
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
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
.;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.77
T;T
M_CAP
Pathogenic
0.43
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.81
T
PrimateAI
Pathogenic
0.90
D
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
D
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.

Other links and lift over

dbSNP: rs932961110; hg19: chr19-812682; API