19-812632-C-G

Variant names:

• chr19-812632-C-G
• rs1185809399
• NM_001270366.2:c.2095G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270366.2(PLPPR3):​c.2095G>C​(p.Glu699Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000312 in 961,436 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. 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. E699K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: PLPPR3 NM_001270366.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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

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=0.104607254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR3	NM_001270366.2	c.2095G>C	p.Glu699Gln	missense_variant	Exon 8 of 8	ENST00000520876.8	NP_001257295.1
PLPPR3	NM_024888.3	c.2179G>C	p.Glu727Gln	missense_variant	Exon 7 of 7		NP_079164.1
PLPPR3	XM_011528317.4	c.2179G>C	p.Glu727Gln	missense_variant	Exon 7 of 7		XP_011526619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPPR3	ENST00000520876.8	c.2095G>C	p.Glu699Gln	missense_variant	Exon 8 of 8	1	NM_001270366.2	ENSP00000430297.1
PLPPR3	ENST00000359894.6	c.2179G>C	p.Glu727Gln	missense_variant	Exon 7 of 7	1		ENSP00000352962.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000312 AC: 3 AN: 961436 Hom.: 0 Cov.: 35 AF XY: 0.00000216 AC XY: 1 AN XY: 463536

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.022	.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.091
Sift	Benign	0.11	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.81	P;B
Vest4		0.15
MutPred		0.26		.;Gain of loop (P = 0.002);
MVP		0.21
MPC		0.46
ClinPred		0.22	T
GERP RS		4.2
Varity_R		0.17
gMVP		0.21

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

Other links and lift over

dbSNP: rs1185809399; hg19: chr19-812632;