NM_005817.5:c.856G>T

Variant names:

• chr19-4844772-C-A
• rs577339133
• NM_005817.5:c.856G>T

Variant summary

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

The NM_005817.5(PLIN3):​c.856G>T​(p.Val286Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000759 in 1,448,954 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: PLIN3 NM_005817.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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 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	c.856G>T	p.Val286Phe	missense_variant	Exon 7 of 8	ENST00000221957.9	NP_005808.3
PLIN3	NM_001164189.2	c.856G>T	p.Val286Phe	missense_variant	Exon 7 of 8		NP_001157661.1
PLIN3	NM_001164194.2	c.820G>T	p.Val274Phe	missense_variant	Exon 7 of 8		NP_001157666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN3	ENST00000221957.9	c.856G>T	p.Val286Phe	missense_variant	Exon 7 of 8	1	NM_005817.5	ENSP00000221957.3
PLIN3	ENST00000585479.5	c.856G>T	p.Val286Phe	missense_variant	Exon 7 of 8	1		ENSP00000465596.1
PLIN3	ENST00000592528.5	c.820G>T	p.Val274Phe	missense_variant	Exon 7 of 8	2		ENSP00000467803.1
PLIN3	ENST00000589163.5	c.427G>T	p.Val143Phe	missense_variant	Exon 4 of 5	3		ENSP00000468476.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000759 AC: 11 AN: 1448954 Hom.: 0 Cov.: 33 AF XY: 0.00000834 AC XY: 6 AN XY: 719576

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000904

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	N;.;.
REVEL	Benign	0.086
Sift	Benign	0.096	T;.;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.041	B;.;B
Vest4		0.50
MutPred		0.70		Loss of ubiquitination at K283 (P = 0.063);.;Loss of ubiquitination at K283 (P = 0.063);
MVP		0.23
MPC		0.26
ClinPred		0.51	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
gMVP		0.22

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

Other links and lift over

dbSNP: rs577339133; hg19: chr19-4844784;