rs1138439

Variant names:

• chr19-282753-G-A
• rs1138439
• NM_003712.4:c.539C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-282753-G-A
• chr19-282753-G-C
• chr19-282753-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003712.4(PLPP2):​c.539C>T​(p.Ala180Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.421 in 1,610,080 control chromosomes in the GnomAD database, including 145,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14655 hom., cov: 30)
  • Exomes 𝑓: 0.42 (130940 hom.)
• Consequence: PLPP2 NM_003712.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001580
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.19
• Publications: 31 publications found

Genes affected

PLPP2 (HGNC:9230): (phospholipid phosphatase 2) The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is similar to phosphatidic acid phosphatase type 2A (PPAP2A) and type 2B (PPAP2B). All three proteins contain 6 transmembrane regions, and a consensus N-glycosylation site. This protein has been shown to possess membrane associated PAP activity. Three alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025349855).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.539C>T	p.Ala180Val	missense_variant, splice_region_variant	Exon 4 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.602C>T	p.Ala201Val	missense_variant, splice_region_variant	Exon 4 of 6		NP_808211.1
PLPP2	NM_177526.3	c.371C>T	p.Ala124Val	missense_variant, splice_region_variant	Exon 4 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.557C>T	p.Ala186Val	missense_variant, splice_region_variant	Exon 4 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.539C>T	p.Ala180Val	missense_variant, splice_region_variant	Exon 4 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65883 AN: 151512 Hom.: 14656 Cov.: 30

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.440

GnomAD2 exomes AF: 0.413 AC: 103318 AN: 249906 AF XY: 0.413

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.419 AC: 611676 AN: 1458450 Hom.: 130940 Cov.: 39 AF XY: 0.419 AC XY: 304096 AN XY: 725694

African (AFR) AF: 0.477 AC: 15912 AN: 33364

American (AMR) AF: 0.414 AC: 18430 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 12404 AN: 26066

East Asian (EAS) AF: 0.153 AC: 6060 AN: 39686

South Asian (SAS) AF: 0.372 AC: 32052 AN: 86178

European-Finnish (FIN) AF: 0.531 AC: 28184 AN: 53098

Middle Eastern (MID) AF: 0.476 AC: 2743 AN: 5758

European-Non Finnish (NFE) AF: 0.424 AC: 470854 AN: 1109528

Other (OTH) AF: 0.415 AC: 25037 AN: 60284

GnomAD4 genome AF: 0.435 AC: 65904 AN: 151630 Hom.: 14655 Cov.: 30 AF XY: 0.436 AC XY: 32309 AN XY: 74140

African (AFR) AF: 0.470 AC: 19391 AN: 41288

American (AMR) AF: 0.411 AC: 6262 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1635 AN: 3466

East Asian (EAS) AF: 0.130 AC: 669 AN: 5158

South Asian (SAS) AF: 0.345 AC: 1650 AN: 4782

European-Finnish (FIN) AF: 0.525 AC: 5536 AN: 10546

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29281 AN: 67858

Other (OTH) AF: 0.438 AC: 922 AN: 2106

Alfa AF: 0.427 Hom.: 30639

Bravo AF: 0.427

TwinsUK AF: 0.425 AC: 1575

ALSPAC AF: 0.417 AC: 1609

ESP6500AA AF: 0.465 AC: 2049

ESP6500EA AF: 0.433 AC: 3724

ExAC AF: 0.411 AC: 49878

Asia WGS AF: 0.280 AC: 975 AN: 3478

EpiCase AF: 0.432

EpiControl AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.71
DEOGEN2	Uncertain	0.56	.;D;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D;D
MetaRNN	Benign	0.0025	T;T;T;T
MetaSVM	Benign	-0.94	T
PhyloP100		6.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.9	D;D;.;.
REVEL	Benign	0.28
Sift	Benign	0.31	T;D;.;.
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.054	B;B;.;.
Vest4		0.14
MPC		0.34
ClinPred		0.049	T
GERP RS		-0.069
Varity_R		0.094
gMVP		0.81
Mutation Taster		=88/12	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.14		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: rs1138439; hg19: chr19-282753; COSMIC: COSV54120817; COSMIC: COSV54120817;