rs763568905

Variant summary

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

The NM_005817.5(PLIN3):​c.1088G>T​(p.Arg363Leu) 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 1,457,374 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R363G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLIN3
NM_005817.5 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.500
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15160426).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLIN3NM_005817.5 linkc.1088G>T p.Arg363Leu missense_variant Exon 8 of 8 ENST00000221957.9 NP_005808.3 O60664-1
PLIN3NM_001164189.2 linkc.1085G>T p.Arg362Leu missense_variant Exon 8 of 8 NP_001157661.1 O60664-3A0A140VJN8
PLIN3NM_001164194.2 linkc.1052G>T p.Arg351Leu missense_variant Exon 8 of 8 NP_001157666.1 O60664-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLIN3ENST00000221957.9 linkc.1088G>T p.Arg363Leu missense_variant Exon 8 of 8 1 NM_005817.5 ENSP00000221957.3 O60664-1
PLIN3ENST00000585479.5 linkc.1085G>T p.Arg362Leu missense_variant Exon 8 of 8 1 ENSP00000465596.1 O60664-3
PLIN3ENST00000592528.5 linkc.1052G>T p.Arg351Leu missense_variant Exon 8 of 8 2 ENSP00000467803.1 O60664-4
PLIN3ENST00000589163.5 linkc.659G>T p.Arg220Leu missense_variant Exon 5 of 5 3 ENSP00000468476.1 K7ERZ3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000804
AC:
2
AN:
248796
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134588
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:
2
AN:
1457374
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
724154
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.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
14
DANN
Benign
0.91
DEOGEN2
Benign
0.16
T;.;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Pathogenic
3.1
M;.;.
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-4.1
D;.;.
REVEL
Benign
0.087
Sift
Benign
0.69
T;.;.
Sift4G
Benign
0.68
T;T;T
Polyphen
0.87
P;.;P
Vest4
0.12
MutPred
0.55
Loss of MoRF binding (P = 0.0708);.;.;
MVP
0.32
MPC
0.21
ClinPred
0.62
D
GERP RS
1.4
Varity_R
0.16
gMVP
0.53

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: rs763568905; hg19: chr19-4839421; COSMIC: COSV104546480; COSMIC: COSV104546480; API