dbSNP rs780194423: PLIN3:p.Arg391Cys (chr19-4839326-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005817.5(PLIN3):c.1171C>T(p.Arg391Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R391G) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PLIN3
NM_005817.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.39

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN3	NM_005817.5 link	c.1171C>T	p.Arg391Cys	missense_variant	Exon 8 of 8	ENST00000221957.9	NP_005808.3	O60664-1
PLIN3	NM_001164189.2 link	c.1168C>T	p.Arg390Cys	missense_variant	Exon 8 of 8		NP_001157661.1	O60664-3A0A140VJN8
PLIN3	NM_001164194.2 link	c.1135C>T	p.Arg379Cys	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.1171C>T	p.Arg391Cys	missense_variant	Exon 8 of 8	1	NM_005817.5	ENSP00000221957.3	O60664-1
PLIN3	ENST00000585479.5 link	c.1168C>T	p.Arg390Cys	missense_variant	Exon 8 of 8	1		ENSP00000465596.1	O60664-3
PLIN3	ENST00000592528.5 link	c.1135C>T	p.Arg379Cys	missense_variant	Exon 8 of 8	2		ENSP00000467803.1	O60664-4
PLIN3	ENST00000589163.5 link	c.742C>T	p.Arg248Cys	missense_variant	Exon 5 of 5	3		ENSP00000468476.1	K7ERZ3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152114

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250682

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

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

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

M;.;.

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-6.6

D;.;.

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.40

MVP

0.38

MPC

0.57

ClinPred

0.87

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over