19-4844774-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005817.5(PLIN3):​c.854G>A​(p.Gly285Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. G285C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLIN3
NM_005817.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.984
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27537346).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLIN3NM_005817.5 linkc.854G>A p.Gly285Asp missense_variant Exon 7 of 8 ENST00000221957.9 NP_005808.3 O60664-1
PLIN3NM_001164189.2 linkc.854G>A p.Gly285Asp missense_variant Exon 7 of 8 NP_001157661.1 O60664-3A0A140VJN8
PLIN3NM_001164194.2 linkc.818G>A p.Gly273Asp missense_variant Exon 7 of 8 NP_001157666.1 O60664-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLIN3ENST00000221957.9 linkc.854G>A p.Gly285Asp missense_variant Exon 7 of 8 1 NM_005817.5 ENSP00000221957.3 O60664-1
PLIN3ENST00000585479.5 linkc.854G>A p.Gly285Asp missense_variant Exon 7 of 8 1 ENSP00000465596.1 O60664-3
PLIN3ENST00000592528.5 linkc.818G>A p.Gly273Asp missense_variant Exon 7 of 8 2 ENSP00000467803.1 O60664-4
PLIN3ENST00000589163.5 linkc.425G>A p.Gly142Asp missense_variant Exon 4 of 5 3 ENSP00000468476.1 K7ERZ3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1448604
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
719410
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000391
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.04e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.854G>A (p.G285D) alteration is located in exon 7 (coding exon 6) of the PLIN3 gene. This alteration results from a G to A substitution at nucleotide position 854, causing the glycine (G) at amino acid position 285 to be replaced by an aspartic acid (D). 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
0.16
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Benign
0.45
DEOGEN2
Benign
0.18
T;.;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.098
N
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.;M
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.4
N;.;.
REVEL
Benign
0.089
Sift
Benign
0.086
T;.;.
Sift4G
Benign
0.16
T;T;T
Polyphen
0.14
B;.;B
Vest4
0.35
MutPred
0.56
Loss of methylation at K283 (P = 0.0438);.;Loss of methylation at K283 (P = 0.0438);
MVP
0.17
MPC
0.25
ClinPred
0.17
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.090
gMVP
0.14

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.

Other links and lift over

dbSNP: rs1421276360; hg19: chr19-4844786; API