19-4844759-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005817.5(PLIN3):ā€‹c.869T>Gā€‹(p.Leu290Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,450,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

PLIN3
NM_005817.5 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLIN3NM_005817.5 linkc.869T>G p.Leu290Arg missense_variant 7/8 ENST00000221957.9 NP_005808.3 O60664-1
PLIN3NM_001164189.2 linkc.869T>G p.Leu290Arg missense_variant 7/8 NP_001157661.1 O60664-3A0A140VJN8
PLIN3NM_001164194.2 linkc.833T>G p.Leu278Arg missense_variant 7/8 NP_001157666.1 O60664-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLIN3ENST00000221957.9 linkc.869T>G p.Leu290Arg missense_variant 7/81 NM_005817.5 ENSP00000221957.3 O60664-1
PLIN3ENST00000585479.5 linkc.869T>G p.Leu290Arg missense_variant 7/81 ENSP00000465596.1 O60664-3
PLIN3ENST00000592528.5 linkc.833T>G p.Leu278Arg missense_variant 7/82 ENSP00000467803.1 O60664-4
PLIN3ENST00000589163.5 linkc.440T>G p.Leu147Arg missense_variant 4/53 ENSP00000468476.1 K7ERZ3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000437
AC:
1
AN:
228858
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
123460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000314
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.00000207
AC:
3
AN:
1450904
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
720716
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000234
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsNov 10, 2024The c.869T>G (p.L290R) alteration is located in exon 7 (coding exon 6) of the PLIN3 gene. This alteration results from a T to G substitution at nucleotide position 869, causing the leucine (L) at amino acid position 290 to be replaced by an arginine (R). 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
0.13
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.2
M;.;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.7
D;.;.
REVEL
Benign
0.14
Sift
Uncertain
0.0050
D;.;.
Sift4G
Uncertain
0.017
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.60
MutPred
0.46
Gain of MoRF binding (P = 0.0247);.;Gain of MoRF binding (P = 0.0247);
MVP
0.43
MPC
0.61
ClinPred
0.91
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.64
gMVP
0.52

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: rs373776545; hg19: chr19-4844771; API