19-4844621-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005817.5(PLIN3):c.960+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,551,118 control chromosomes in the GnomAD database, including 59,752 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4579 hom., cov: 31)
  • Exomes 𝑓: 0.28 (55173 hom.)
• Consequence: PLIN3 NM_005817.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN3	NM_005817.5	c.960+47G>A		intron_variant		ENST00000221957.9
PLIN3	NM_001164189.2	c.960+47G>A		intron_variant
PLIN3	NM_001164194.2	c.924+47G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN3	ENST00000221957.9	c.960+47G>A		intron_variant		1	NM_005817.5	P3
PLIN3	ENST00000585479.5	c.960+47G>A		intron_variant		1		A1
PLIN3	ENST00000589163.5	c.533+47G>A		intron_variant		3
PLIN3	ENST00000592528.5	c.924+47G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 35761 AN: 149122 Hom.: 4579 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.283 AC: 50319 AN: 177610 Hom.: 6743 AF XY: 0.284 AC XY: 27159 AN XY: 95748

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.337

Gnomad SAS exome AF: 0.257

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.278 AC: 390100 AN: 1401878 Hom.: 55173 Cov.: 28 AF XY: 0.277 AC XY: 192107 AN XY: 693840

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.240 AC: 35760 AN: 149240 Hom.: 4579 Cov.: 31 AF XY: 0.238 AC XY: 17304 AN XY: 72754

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.261

Alfa AF: 0.262 Hom.: 5987

Bravo AF: 0.238

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.3
Dann	Benign	0.77

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: rs17363814; hg19: chr19-4844633; COSMIC: COSV99701504;