Genetic Variant PLPPR3:p.Glu603Asp (chr19-812918-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001270366.2(PLPPR3):c.1809G>C(p.Glu603Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,174,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PLPPR3
NM_001270366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.480

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3552111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR3	NM_001270366.2 link	c.1809G>C	p.Glu603Asp	missense_variant	Exon 8 of 8	ENST00000520876.8	NP_001257295.1	Q6T4P5-1
PLPPR3	NM_024888.3 link	c.1893G>C	p.Glu631Asp	missense_variant	Exon 7 of 7		NP_079164.1	Q6T4P5-3
PLPPR3	XM_011528317.4 link	c.1893G>C	p.Glu631Asp	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.1809G>C	p.Glu603Asp	missense_variant	Exon 8 of 8	1	NM_001270366.2	ENSP00000430297.1		Q6T4P5-1
PLPPR3	ENST00000359894.6 link	c.1893G>C	p.Glu631Asp	missense_variant	Exon 7 of 7	1		ENSP00000352962.2		Q6T4P5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

41634

Hom.:

AF XY:

0.00

AC XY:

AN XY:

25650

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:

0.0000562

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1174164

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

576730

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:

0.0000124

Gnomad4 OTH exome

AF:

0.0000883

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1893G>C (p.E631D) 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 1893, causing the glutamic acid (E) at amino acid position 631 to be replaced by an aspartic acid (D). 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

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.085

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.10

Sift

Benign

0.057

T;T

Sift4G

Benign

0.15

T;T

Polyphen

1.0

D;D

Vest4

0.43

MutPred

0.16

.;Loss of helix (P = 0.0558);

MVP

0.36

MPC

1.1

ClinPred

0.40

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.095

gMVP

0.16

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