rs914830

Positions:

• chr1-56578658-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003713.5(PLPP3):​c.139+220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,060 control chromosomes in the GnomAD database, including 14,144 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 0.40 (14144 hom., cov: 32)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.139+220G>A		intron_variant		ENST00000371250.4	NP_003704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPP3	ENST00000371250.4	c.139+220G>A		intron_variant		1	NM_003713.5	ENSP00000360296	P1
PLPP3	ENST00000461655.1	n.242-41546G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61103 AN: 151942 Hom.: 14133 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.402 AC: 61114 AN: 152060 Hom.: 14144 Cov.: 32 AF XY: 0.399 AC XY: 29699 AN XY: 74362

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.405

Alfa AF: 0.453 Hom.: 2097

Bravo AF: 0.400

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.78

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: rs914830; hg19: chr1-57044331;