19-4847875-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_005817.5(PLIN3):c.650C>G(p.Ser217Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLIN3 NM_005817.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity PLIN3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32776764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN3	NM_005817.5	c.650C>G	p.Ser217Cys	missense_variant	6/8	ENST00000221957.9
PLIN3	NM_001164189.2	c.650C>G	p.Ser217Cys	missense_variant	6/8
PLIN3	NM_001164194.2	c.614C>G	p.Ser205Cys	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN3	ENST00000221957.9	c.650C>G	p.Ser217Cys	missense_variant	6/8	1	NM_005817.5	P3
PLIN3	ENST00000585479.5	c.650C>G	p.Ser217Cys	missense_variant	6/8	1		A1
PLIN3	ENST00000592528.5	c.614C>G	p.Ser205Cys	missense_variant	6/8	2
PLIN3	ENST00000589163.5	c.350C>G	p.Ser117Cys	missense_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2021

The c.650C>G (p.S217C) alteration is located in exon 6 (coding exon 5) of the PLIN3 gene. This alteration results from a C to G substitution at nucleotide position 650, causing the serine (S) at amino acid position 217 to be replaced by a cysteine (C). 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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	25
Dann	Uncertain	0.97
DEOGEN2	Benign	0.22	T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;.;M
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.6	D;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.026	D;.;.
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.36
MutPred		0.49		Gain of catalytic residue at L218 (P = 0.0175);.;Gain of catalytic residue at L218 (P = 0.0175);
MVP		0.28
MPC		0.47
ClinPred		0.98	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4847887;