19-812739-G-A

Variant names:

• chr19-812739-G-A
• rs1001609628
• NM_001270366.2:c.1988C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001270366.2(PLPPR3):​c.1988C>T​(p.Thr663Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000842 in 1,068,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T663A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: PLPPR3 NM_001270366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26639092).

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.1988C>T	p.Thr663Met	missense	Exon 8 of 8	NP_001257295.1	Q6T4P5-1
	PLPPR3	NM_024888.3		c.2072C>T	p.Thr691Met	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.1988C>T	p.Thr663Met	missense	Exon 8 of 8	ENSP00000430297.1	Q6T4P5-1
	PLPPR3	ENST00000359894.6	TSL:1	c.2072C>T	p.Thr691Met	missense	Exon 7 of 7	ENSP00000352962.2	Q6T4P5-3
	PLPPR3	ENST00000947290.1		c.2072C>T	p.Thr691Met	missense	Exon 6 of 6	ENSP00000617349.1

Frequencies

GnomAD3 genomes AF: 0.000395 AC: 58 AN: 146928 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000203

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: 0.00

Gnomad OTH AF: 0.000493

GnomAD4 exome AF: 0.0000336 AC: 31 AN: 921614 Hom.: 0 Cov.: 34 AF XY: 0.0000371 AC XY: 16 AN XY: 431588

African (AFR) AF: 0.00111 AC: 19 AN: 17194

American (AMR) AF: 0.00 AC: 0 AN: 3388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7286

East Asian (EAS) AF: 0.00 AC: 0 AN: 11020

South Asian (SAS) AF: 0.0000544 AC: 1 AN: 18392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2026

European-Non Finnish (NFE) AF: 0.00000612 AC: 5 AN: 816938

Other (OTH) AF: 0.000186 AC: 6 AN: 32330

GnomAD4 genome AF: 0.000401 AC: 59 AN: 147020 Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 27 AN XY: 71616

African (AFR) AF: 0.00134 AC: 55 AN: 41054

American (AMR) AF: 0.000203 AC: 3 AN: 14806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66018

Other (OTH) AF: 0.000488 AC: 1 AN: 2048

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000404

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.17		Loss of sheet (P = 0.0084)
MVP		0.61
MPC		1.2
ClinPred		0.89	D
GERP RS		4.6
Varity_R		0.076
gMVP		0.34
Mutation Taster		=97/3	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: rs1001609628; hg19: chr19-812739;