rs12566304

Positions:

• chr1-56570684-C-A
• chr1-56570684-C-G
• chr1-56570684-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+8194G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,042 control chromosomes in the GnomAD database, including 6,812 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 0.28 (6812 hom., cov: 32)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.139+8194G>T		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+8194G>T		intron_variant		1	NM_003713.5	ENSP00000360296	P1
PLPP3	ENST00000461655.1	n.242-33572G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42476 AN: 151924 Hom.: 6812 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.279 AC: 42468 AN: 152042 Hom.: 6812 Cov.: 32 AF XY: 0.280 AC XY: 20811 AN XY: 74310

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.311

Alfa AF: 0.201 Hom.: 490

Bravo AF: 0.264

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.80

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: rs12566304; hg19: chr1-57036357; COSMIC: COSV64838988;