Variant 1-56524535-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_003713.5(PLPP3):c.317A>G(p.Tyr106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLPP3
NM_003713.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

Variant links:

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 links:

PLPP3 (HGNC:):

PLPP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a mutagenesis_site No effect on basolateral localization in polarized cells. (size 0) in uniprot entity PLPP3_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP3	NM_003713.5 linkuse as main transcript	c.317A>G	p.Tyr106Cys	missense_variant	3/6	ENST00000371250.4	NP_003704.3	O14495

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLPP3	ENST00000371250.4 linkuse as main transcript	c.317A>G	p.Tyr106Cys	missense_variant	3/6	1	NM_003713.5	ENSP00000360296.3	O14495
PLPP3	ENST00000461655.1 linkuse as main transcript	n.419A>G		non_coding_transcript_exon_variant	4/4	3
ENSG00000284686	ENST00000642129.1 linkuse as main transcript	n.-41A>G		upstream_gene_variant				ENSP00000492927.1	A0A286YES4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248638

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458192

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.317A>G (p.Y106C) alteration is located in exon 3 (coding exon 3) of the PLPP3 gene. This alteration results from a A to G substitution at nucleotide position 317, causing the tyrosine (Y) at amino acid position 106 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.78

MetaSVM

Uncertain

0.0046

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.59

Sift

Uncertain

0.027

Sift4G

Uncertain

0.052

Polyphen

0.99

Vest4

0.91

MutPred

0.38

Loss of sheet (P = 0.0315);

MVP

0.65

MPC

1.6

ClinPred

0.96

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over