Genetic Variant PLIN3:p.Arg363Gly (chr19-4839410-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005817.5(PLIN3):c.1087C>G(p.Arg363Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R363H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

PLIN3
NM_005817.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0980

Variant links:

Genes affected

PLIN3 (HGNC:16893): (perilipin 3) Mannose 6-phophate receptors (MPRs) deliver lysosomal hydrolase from the Golgi to endosomes and then return to the Golgi complex. The protein encoded by this gene interacts with the cytoplasmic domains of both cation-independent and cation-dependent MPRs, and is required for endosome-to-Golgi transport. This protein also binds directly to the GTPase RAB9 (RAB9A), a member of the RAS oncogene family. The interaction with RAB9 has been shown to increase the affinity of this protein for its cargo. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2009]

PLIN3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18245274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN3	NM_005817.5 link	c.1087C>G	p.Arg363Gly	missense_variant	Exon 8 of 8	ENST00000221957.9	NP_005808.3	O60664-1
PLIN3	NM_001164189.2 link	c.1084C>G	p.Arg362Gly	missense_variant	Exon 8 of 8		NP_001157661.1	O60664-3A0A140VJN8
PLIN3	NM_001164194.2 link	c.1051C>G	p.Arg351Gly	missense_variant	Exon 8 of 8		NP_001157666.1	O60664-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLIN3	ENST00000221957.9 link	c.1087C>G	p.Arg363Gly	missense_variant	Exon 8 of 8	1	NM_005817.5	ENSP00000221957.3	O60664-1
PLIN3	ENST00000585479.5 link	c.1084C>G	p.Arg362Gly	missense_variant	Exon 8 of 8	1		ENSP00000465596.1	O60664-3
PLIN3	ENST00000592528.5 link	c.1051C>G	p.Arg351Gly	missense_variant	Exon 8 of 8	2		ENSP00000467803.1	O60664-4
PLIN3	ENST00000589163.5 link	c.658C>G	p.Arg220Gly	missense_variant	Exon 5 of 5	3		ENSP00000468476.1	K7ERZ3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1087C>G (p.R363G) alteration is located in exon 8 (coding exon 7) of the PLIN3 gene. This alteration results from a C to G substitution at nucleotide position 1087, causing the arginine (R) at amino acid position 363 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.16

T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.2

D;.;.

REVEL

Benign

0.10

Sift

Benign

0.61

T;.;.

Sift4G

Benign

0.51

T;T;T

Polyphen

0.93

P;.;P

Vest4

0.13

MutPred

0.57

Loss of stability (P = 0.0518);.;.;

MVP

0.32

MPC

0.46

ClinPred

0.86

GERP RS

3.9

Varity_R

0.11

gMVP

0.50

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