19-812847-C-A

Variant names:

• chr19-812847-C-A
• rs1311030776
• NM_001270366.2:c.1880G>T

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.1880G>T​(p.Gly627Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,142,092 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. 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. G627D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: PLPPR3 NM_001270366.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 1 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=0.109298766).

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.1880G>T	p.Gly627Val	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.1964G>T	p.Gly655Val	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.1880G>T	p.Gly627Val	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
	PLPPR3	ENST00000359894.6	TSL:1	c.1964G>T	p.Gly655Val	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
	PLPPR3	ENST00000947290.1		c.1964G>T	p.Gly655Val	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes AF: 0.00000680 AC: 1 AN: 147068 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: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000100 AC: 1 AN: 995024 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 473930

African (AFR) AF: 0.00 AC: 0 AN: 18266

American (AMR) AF: 0.00 AC: 0 AN: 4564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8988

East Asian (EAS) AF: 0.00 AC: 0 AN: 14046

South Asian (SAS) AF: 0.00 AC: 0 AN: 29840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2346

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 862154

Other (OTH) AF: 0.00 AC: 0 AN: 36074

GnomAD4 genome AF: 0.00000680 AC: 1 AN: 147068 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71570

African (AFR) AF: 0.00 AC: 0 AN: 40894

American (AMR) AF: 0.00 AC: 0 AN: 14814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66078

Other (OTH) AF: 0.00 AC: 0 AN: 2020

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.45
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.038
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.054	T
Polyphen		0.79	P
Vest4		0.13
MutPred		0.36		Gain of helix (P = 0.0117)
MVP		0.25
MPC		0.94
ClinPred		0.88	D
GERP RS		2.4
Varity_R		0.19
gMVP		0.19
Mutation Taster		=96/4	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: rs1311030776; hg19: chr19-812847;