19-812632-C-T

Variant names:

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

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>A​(p.Glu699Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLPPR3 NM_001270366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.10937804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR3	NM_001270366.2	c.2095G>A	p.Glu699Lys	missense_variant	Exon 8 of 8	ENST00000520876.8	NP_001257295.1
PLPPR3	NM_024888.3	c.2179G>A	p.Glu727Lys	missense_variant	Exon 7 of 7		NP_079164.1
PLPPR3	XM_011528317.4	c.2179G>A	p.Glu727Lys	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>A	p.Glu699Lys	missense_variant	Exon 8 of 8	1	NM_001270366.2	ENSP00000430297.1
PLPPR3	ENST00000359894.6	c.2179G>A	p.Glu727Lys	missense_variant	Exon 7 of 7	1		ENSP00000352962.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 961436 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2179G>A (p.E727K) alteration is located in exon 7 (coding exon 6) of the PLPPR3 gene. This alteration results from a G to A substitution at nucleotide position 2179, causing the glutamic acid (E) at amino acid position 727 to be replaced by a lysine (K). 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	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.086
Sift	Benign	0.11	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.82	P;B
Vest4		0.18
MutPred		0.32		.;Gain of loop (P = 3e-04);
MVP		0.31
MPC		0.46
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.20
gMVP		0.22

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;