rs914830

Variant names:

• chr1-56578658-C-T
• rs914830
• NM_003713.5:c.139+220G>A

Variant summary

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

The NM_003713.5(PLPP3):​c.139+220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,060 control chromosomes in the GnomAD database, including 14,144 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 0.40 (14144 hom., cov: 32)
• Consequence: PLPP3 NM_003713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP3	NM_003713.5	c.139+220G>A		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.139+220G>A		intron_variant	Intron 1 of 5	1	NM_003713.5	ENSP00000360296.3
PLPP3	ENST00000461655.1	n.242-41546G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61103 AN: 151942 Hom.: 14133 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.402 AC: 61114 AN: 152060 Hom.: 14144 Cov.: 32 AF XY: 0.399 AC XY: 29699 AN XY: 74362

African (AFR) AF: 0.166 AC: 6876 AN: 41530

American (AMR) AF: 0.542 AC: 8278 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1672 AN: 5134

South Asian (SAS) AF: 0.337 AC: 1625 AN: 4824

European-Finnish (FIN) AF: 0.472 AC: 4986 AN: 10562

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.507 AC: 34471 AN: 67956

Other (OTH) AF: 0.405 AC: 854 AN: 2110

Alfa AF: 0.442 Hom.: 2109

Bravo AF: 0.400

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		3.3
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: rs914830; hg19: chr1-57044331;