1-56527743-G-C

Variant names:

• chr1-56527743-G-C
• rs1759752
• NM_003713.5:c.298-3189C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003713.5(PLPP3):​c.298-3189C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,864 control chromosomes in the GnomAD database, including 16,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (16840 hom., cov: 31)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 8 publications found

Genes affected

PLPP3 (HGNC:9229): (phospholipid phosphatase 3) 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 a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid and short-chain phosphatidic acid. The expression of this gene is found to be enhanced by epidermal growth factor in Hela cells. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.298-3189C>G		intron_variant	Intron 2 of 5	ENST00000371250.4	NP_003704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP3	ENST00000371250.4	c.298-3189C>G		intron_variant	Intron 2 of 5	1	NM_003713.5	ENSP00000360296.3
PLPP3	ENST00000461655.1	n.400-3189C>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70830 AN: 151746 Hom.: 16812 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 70919 AN: 151864 Hom.: 16840 Cov.: 31 AF XY: 0.464 AC XY: 34401 AN XY: 74206

African (AFR) AF: 0.534 AC: 22110 AN: 41382

American (AMR) AF: 0.458 AC: 6995 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1228 AN: 5154

South Asian (SAS) AF: 0.418 AC: 2010 AN: 4810

European-Finnish (FIN) AF: 0.460 AC: 4846 AN: 10540

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30862 AN: 67930

Other (OTH) AF: 0.463 AC: 978 AN: 2114

Alfa AF: 0.317 Hom.: 741

Bravo AF: 0.468

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.66
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs1759752; hg19: chr1-56993415;