chr1-56551239-A-C

Variant names:

• chr1-56551239-A-C
• rs10493211
• NM_003713.5:c.140-14127T>G

Variant summary

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

The NM_003713.5(PLPP3):​c.140-14127T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 145,058 control chromosomes in the GnomAD database, including 6,999 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 0.30 (6999 hom., cov: 29)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.140-14127T>G		intron_variant	Intron 1 of 5	ENST00000371250.4	NP_003704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP3	ENST00000371250.4	c.140-14127T>G		intron_variant	Intron 1 of 5	1	NM_003713.5	ENSP00000360296.3
PLPP3	ENST00000461655.1	n.242-14127T>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 43209 AN: 144956 Hom.: 6985 Cov.: 29

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.298 AC: 43264 AN: 145058 Hom.: 6999 Cov.: 29 AF XY: 0.294 AC XY: 20740 AN XY: 70584

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0901

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.306

Alfa AF: 0.319 Hom.: 10656

Bravo AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.55

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: rs10493211; hg19: chr1-57016912;