19-812820-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001270366.2(PLPPR3):​c.1907G>C​(p.Gly636Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,107,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

PLPPR3
NM_001270366.2 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22399789).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLPPR3NM_001270366.2 linkc.1907G>C p.Gly636Ala missense_variant Exon 8 of 8 ENST00000520876.8 NP_001257295.1 Q6T4P5-1
PLPPR3NM_024888.3 linkc.1991G>C p.Gly664Ala missense_variant Exon 7 of 7 NP_079164.1 Q6T4P5-3
PLPPR3XM_011528317.4 linkc.1991G>C p.Gly664Ala 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.1907G>C p.Gly636Ala missense_variant Exon 8 of 8 1 NM_001270366.2 ENSP00000430297.1 Q6T4P5-1
PLPPR3ENST00000359894.6 linkc.1991G>C p.Gly664Ala missense_variant Exon 7 of 7 1 ENSP00000352962.2 Q6T4P5-3

Frequencies

GnomAD3 genomes
AF:
0.0000951
AC:
14
AN:
147164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000293
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000135
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000521
AC:
5
AN:
960420
Hom.:
0
Cov.:
34
AF XY:
0.00000662
AC XY:
3
AN XY:
453468
show subpopulations
Gnomad4 AFR exome
AF:
0.000225
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:
0.00
Gnomad4 OTH exome
AF:
0.0000291
GnomAD4 genome
AF:
0.0000951
AC:
14
AN:
147164
Hom.:
0
Cov.:
32
AF XY:
0.0000977
AC XY:
7
AN XY:
71624
show subpopulations
Gnomad4 AFR
AF:
0.000293
Gnomad4 AMR
AF:
0.000135
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000102

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1991G>C (p.G664A) 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 1991, causing the glycine (G) at amino acid position 664 to be replaced by an alanine (A). 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
0.090
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
.;T
Eigen
Benign
0.026
Eigen_PC
Benign
-0.036
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.16
Sift
Benign
0.47
T;T
Sift4G
Benign
0.51
T;T
Polyphen
1.0
D;D
Vest4
0.32
MutPred
0.13
.;Loss of catalytic residue at G636 (P = 0.0212);
MVP
0.33
MPC
0.51
ClinPred
0.60
D
GERP RS
4.6
Varity_R
0.13
gMVP
0.15

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: rs987097379; hg19: chr19-812820; API