19-812632-C-A

Variant names:

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

Variant summary

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

The NM_001270366.2(PLPPR3):​c.2095G>T​(p.Glu699*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000104 in 961,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: PLPPR3 NM_001270366.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2095G>T	p.Glu699*	stop_gained	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.2179G>T	p.Glu727*	stop_gained	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.2095G>T	p.Glu699*	stop_gained	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
	PLPPR3	ENST00000359894.6	TSL:1	c.2179G>T	p.Glu727*	stop_gained	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
	PLPPR3	ENST00000947290.1		c.2179G>T	p.Glu727*	stop_gained	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 961436 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 463536

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17286

American (AMR) AF: 0.00 AC: 0 AN: 6252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9166

East Asian (EAS) AF: 0.00 AC: 0 AN: 7604

South Asian (SAS) AF: 0.00 AC: 0 AN: 41124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2094

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 833446

Other (OTH) AF: 0.00 AC: 0 AN: 32944

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Uncertain	0.42
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.098	N
PhyloP100		3.7
Vest4		0.053
GERP RS		4.2
Mutation Taster		=66/134	disease causing

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: rs1185809399; hg19: chr19-812632;