Genetic Variant PLPPR3:p.Glu650Lys (chr19-812779-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001270366.2(PLPPR3):c.1948G>A(p.Glu650Lys) 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 147,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E650Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Consequence

PLPPR3
NM_001270366.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.16

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10434064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270366.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR3	NM_001270366.2	MANE Select	c.1948G>A	p.Glu650Lys	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.2032G>A	p.Glu678Lys	missense	Exon 7 of 7	NP_079164.1	Q6T4P5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPPR3	ENST00000520876.8	TSL:1 MANE Select	c.1948G>A	p.Glu650Lys	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
PLPPR3	ENST00000359894.6	TSL:1	c.2032G>A	p.Glu678Lys	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
PLPPR3	ENST00000947290.1		c.2032G>A	p.Glu678Lys	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000136

AC:

AN:

147066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40974

American (AMR)

AF:

0.00

AC:

AN:

14802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

66068

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

M_CAP

Benign

0.047

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.99

PhyloP100

2.2

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Uncertain

0.0040

Sift4G

Benign

0.26

Polyphen

0.0040

Vest4

0.22

MutPred

0.17

Gain of ubiquitination at E650 (P = 9e-04)

MVP

0.26

MPC

1.2

ClinPred

0.85

GERP RS

1.3

Varity_R

0.077

gMVP

0.25

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over