rs10736393

Positions:

• chr1-56558259-A-C
• chr1-56558259-A-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+20619T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,170 control chromosomes in the GnomAD database, including 53,873 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 0.84 (53873 hom., cov: 32)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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]

PLPP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.139+20619T>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.139+20619T>G		intron_variant		1	NM_003713.5	ENSP00000360296.3
PLPP3	ENST00000461655.1	n.242-21147T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127263 AN: 152052 Hom.: 53838 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.837 AC: 127352 AN: 152170 Hom.: 53873 Cov.: 32 AF XY: 0.837 AC XY: 62244 AN XY: 74408

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.855

Alfa AF: 0.875 Hom.: 10188

Bravo AF: 0.832

Asia WGS AF: 0.743 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.9
DANN	Benign	0.57

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: rs10736393; hg19: chr1-57023932;