chr1-56527743-G-C

Position:

• chr1-56527743-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.298-3189C>G		intron_variant		ENST00000371250.4	NP_003704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPP3	ENST00000371250.4	c.298-3189C>G		intron_variant		1	NM_003713.5	ENSP00000360296	P1
PLPP3	ENST00000461655.1	n.400-3189C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.463

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1759752; hg19: chr1-56993415;