19-812820-C-T

Variant names:

• chr19-812820-C-T
• rs987097379
• NM_001270366.2:c.1907G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001270366.2(PLPPR3):​c.1907G>A​(p.Gly636Asp) 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. 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29202038).

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>A	p.Gly636Asp	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.1991G>A	p.Gly664Asp	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.1907G>A	p.Gly636Asp	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
	PLPPR3	ENST00000359894.6	TSL:1	c.1991G>A	p.Gly664Asp	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
	PLPPR3	ENST00000947290.1		c.1991G>A	p.Gly664Asp	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 960420 Hom.: 0 Cov.: 34 AF XY: 0.00000221 AC XY: 1 AN XY: 453468

African (AFR) AF: 0.00 AC: 0 AN: 17770

American (AMR) AF: 0.00 AC: 0 AN: 4068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8246

East Asian (EAS) AF: 0.00 AC: 0 AN: 12960

South Asian (SAS) AF: 0.00 AC: 0 AN: 23442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2204

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841082

Other (OTH) AF: 0.00 AC: 0 AN: 34420

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.022
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.94	T
PhyloP100		2.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Benign	0.16	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.17		Loss of catalytic residue at G636 (P = 0.0153)
MVP		0.44
MPC		0.90
ClinPred		0.75	D
GERP RS		4.6
Varity_R		0.13
gMVP		0.15
Mutation Taster		=92/8	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: rs987097379; hg19: chr19-812820;