19-812638-C-G

Variant names:

• chr19-812638-C-G
• rs1426684447
• NM_001270366.2:c.2089G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270366.2(PLPPR3):​c.2089G>C​(p.Glu697Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,098,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLPPR3 NM_001270366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

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]

ACMG classification

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=0.1331833).

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.2089G>C	p.Glu697Gln	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.2173G>C	p.Glu725Gln	missense	Exon 7 of 7	NP_079164.1	Q6T4P5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR3	ENST00000520876.8	TSL:1 MANE Select	c.2089G>C	p.Glu697Gln	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
	PLPPR3	ENST00000359894.6	TSL:1	c.2173G>C	p.Glu725Gln	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
	PLPPR3	ENST00000947290.1		c.2173G>C	p.Glu725Gln	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 146138 Hom.: 0 Cov.: 32

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: 0.0000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 2 AN: 952372 Hom.: 0 Cov.: 35 AF XY: 0.00000218 AC XY: 1 AN XY: 457912

African (AFR) AF: 0.00 AC: 0 AN: 17118

American (AMR) AF: 0.00 AC: 0 AN: 5074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8630

East Asian (EAS) AF: 0.00 AC: 0 AN: 7744

South Asian (SAS) AF: 0.00 AC: 0 AN: 38342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2048

European-Non Finnish (NFE) AF: 0.00000241 AC: 2 AN: 829562

Other (OTH) AF: 0.00 AC: 0 AN: 32564

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 146138 Hom.: 0 Cov.: 32 AF XY: 0.0000141 AC XY: 1 AN XY: 71038

African (AFR) AF: 0.00 AC: 0 AN: 40798

American (AMR) AF: 0.00 AC: 0 AN: 14712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000304 AC: 2 AN: 65764

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.077
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.024	D
Polyphen		0.74	P
Vest4		0.19
MutPred		0.25		Gain of loop (P = 0.002)
MVP		0.24
MPC		0.47
ClinPred		0.29	T
GERP RS		4.3
Varity_R		0.21
gMVP		0.26
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1426684447; hg19: chr19-812638;