1-56500678-A-G

Position:

• chr1-56500678-A-G

Variant summary

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

The NM_003713.5(PLPP3):​c.811-4002T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,190 control chromosomes in the GnomAD database, including 1,256 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 0.12 (1256 hom., cov: 32)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.811-4002T>C		intron_variant		ENST00000371250.4	NP_003704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPP3	ENST00000371250.4	c.811-4002T>C		intron_variant		1	NM_003713.5	ENSP00000360296	P1
PLPP3	ENST00000459962.1	n.1797-4002T>C		intron_variant, non_coding_transcript_variant		2
PLPP3	ENST00000472957.1	n.296-4002T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18193 AN: 152072 Hom.: 1251 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.0282

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.120 AC: 18225 AN: 152190 Hom.: 1256 Cov.: 32 AF XY: 0.118 AC XY: 8797 AN XY: 74416

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0934 Hom.: 1363

Bravo AF: 0.123

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.26

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: rs17114046; hg19: chr1-56966350;