chr19-4847813-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005817.5(PLIN3):c.712C>T(p.Arg238Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,613,808 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 1 hom. )
Consequence
PLIN3
NM_005817.5 missense
NM_005817.5 missense
Scores
4
11
4
Clinical Significance
Conservation
PhyloP100: 7.43
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.845
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLIN3 | NM_005817.5 | c.712C>T | p.Arg238Cys | missense_variant | 6/8 | ENST00000221957.9 | |
PLIN3 | NM_001164189.2 | c.712C>T | p.Arg238Cys | missense_variant | 6/8 | ||
PLIN3 | NM_001164194.2 | c.676C>T | p.Arg226Cys | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLIN3 | ENST00000221957.9 | c.712C>T | p.Arg238Cys | missense_variant | 6/8 | 1 | NM_005817.5 | P3 | |
PLIN3 | ENST00000585479.5 | c.712C>T | p.Arg238Cys | missense_variant | 6/8 | 1 | A1 | ||
PLIN3 | ENST00000592528.5 | c.676C>T | p.Arg226Cys | missense_variant | 6/8 | 2 | |||
PLIN3 | ENST00000589163.5 | c.407+4C>T | splice_donor_region_variant, intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152122Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000156 AC: 39AN: 250230Hom.: 1 AF XY: 0.000199 AC XY: 27AN XY: 135520
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GnomAD4 exome AF: 0.000168 AC: 245AN: 1461568Hom.: 1 Cov.: 50 AF XY: 0.000197 AC XY: 143AN XY: 727094
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74436
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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 | Dec 05, 2022 | The c.712C>T (p.R238C) alteration is located in exon 6 (coding exon 5) of the PLIN3 gene. This alteration results from a C to T substitution at nucleotide position 712, causing the arginine (R) at amino acid position 238 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.;H
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Uncertain
Sift
Pathogenic
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
P;.;B
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at