1-56541867-T-C

Variant names:

• chr1-56541867-T-C
• rs1930760
• NM_003713.5:c.140-4755A>G

Variant summary

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

The NM_003713.5(PLPP3):​c.140-4755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,582 control chromosomes in the GnomAD database, including 14,447 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 0.43 (14447 hom., cov: 30)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003713.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP3	NM_003713.5	MANE Select	c.140-4755A>G		intron	N/A	NP_003704.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP3	ENST00000371250.4	TSL:1 MANE Select	c.140-4755A>G		intron	N/A	ENSP00000360296.3
	PLPP3	ENST00000461655.1	TSL:3	n.242-4755A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64385 AN: 151466 Hom.: 14412 Cov.: 30

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.425 AC: 64472 AN: 151582 Hom.: 14447 Cov.: 30 AF XY: 0.426 AC XY: 31548 AN XY: 74018

African (AFR) AF: 0.535 AC: 22112 AN: 41318

American (AMR) AF: 0.508 AC: 7728 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2879 AN: 5124

South Asian (SAS) AF: 0.519 AC: 2486 AN: 4786

European-Finnish (FIN) AF: 0.331 AC: 3464 AN: 10462

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23609 AN: 67894

Other (OTH) AF: 0.408 AC: 857 AN: 2098

Alfa AF: 0.375 Hom.: 46846

Bravo AF: 0.444

Asia WGS AF: 0.526 AC: 1830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.62
PhyloP100		0.15
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: rs1930760; hg19: chr1-57007539;