rs763568905

Variant names:

• chr19-4839409-C-A
• rs763568905
• NM_005817.5:c.1088G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-4839409-C-A
• chr19-4839409-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500

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 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
PLIN3	NM_005817.5	c.1088G>T	p.Arg363Leu	missense_variant	Exon 8 of 8	ENST00000221957.9	NP_005808.3
PLIN3	NM_001164189.2	c.1085G>T	p.Arg362Leu	missense_variant	Exon 8 of 8		NP_001157661.1
PLIN3	NM_001164194.2	c.1052G>T	p.Arg351Leu	missense_variant	Exon 8 of 8		NP_001157666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN3	ENST00000221957.9	c.1088G>T	p.Arg363Leu	missense_variant	Exon 8 of 8	1	NM_005817.5	ENSP00000221957.3
PLIN3	ENST00000585479.5	c.1085G>T	p.Arg362Leu	missense_variant	Exon 8 of 8	1		ENSP00000465596.1
PLIN3	ENST00000592528.5	c.1052G>T	p.Arg351Leu	missense_variant	Exon 8 of 8	2		ENSP00000467803.1
PLIN3	ENST00000589163.5	c.659G>T	p.Arg220Leu	missense_variant	Exon 5 of 5	3		ENSP00000468476.1

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

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

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

Other links and lift over

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