Genetic Variant NM_001270366.2:c.1907G>T (chr19-812820-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001270366.2(PLPPR3):c.1907G>T(p.Gly636Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 960,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G636A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

PLPPR3
NM_001270366.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.73

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33039868).

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.1907G>T	p.Gly636Val	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.1991G>T	p.Gly664Val	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.1907G>T	p.Gly636Val	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
PLPPR3	ENST00000359894.6	TSL:1	c.1991G>T	p.Gly664Val	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
PLPPR3	ENST00000947290.1		c.1991G>T	p.Gly664Val	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000104

AC:

AN:

960420

Hom.:

Cov.:

AF XY:

0.00000221

AC XY:

AN XY:

453468

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

17770

American (AMR)

AF:

0.00

AC:

AN:

4068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8246

East Asian (EAS)

AF:

0.00

AC:

AN:

12960

South Asian (SAS)

AF:

0.0000427

AC:

AN:

23442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2204

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841082

Other (OTH)

AF:

0.00

AC:

AN:

34420

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

0.080

Eigen_PC

Benign

0.0016

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

PhyloP100

2.7

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.26

Sift

Benign

0.15

Sift4G

Benign

0.50

Polyphen

1.0

Vest4

0.33

MutPred

0.11

Loss of catalytic residue at G636 (P = 0.0356)

MVP

0.53

MPC

1.0

ClinPred

0.91

GERP RS

4.6

Varity_R

0.25

gMVP

0.23

Mutation Taster

=93/7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over