19-4844621-C-T

Variant names:

• chr19-4844621-C-T
• rs17363814
• NM_005817.5:c.960+47G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLIN3	NM_005817.5	c.960+47G>A		intron_variant	Intron 7 of 7	ENST00000221957.9	NP_005808.3
PLIN3	NM_001164189.2	c.960+47G>A		intron_variant	Intron 7 of 7		NP_001157661.1
PLIN3	NM_001164194.2	c.924+47G>A		intron_variant	Intron 7 of 7		NP_001157666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLIN3	ENST00000221957.9	c.960+47G>A		intron_variant	Intron 7 of 7	1	NM_005817.5	ENSP00000221957.3
PLIN3	ENST00000585479.5	c.960+47G>A		intron_variant	Intron 7 of 7	1		ENSP00000465596.1
PLIN3	ENST00000592528.5	c.924+47G>A		intron_variant	Intron 7 of 7	2		ENSP00000467803.1
PLIN3	ENST00000589163.5	c.531+47G>A		intron_variant	Intron 4 of 4	3		ENSP00000468476.1

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

GnomAD2 exomes AF: 0.283 AC: 50319 AN: 177610 AF XY: 0.284

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 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

African (AFR) AF: 0.122 AC: 3856 AN: 31534

American (AMR) AF: 0.303 AC: 10592 AN: 34962

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 6537 AN: 22868

East Asian (EAS) AF: 0.386 AC: 14884 AN: 38590

South Asian (SAS) AF: 0.228 AC: 17818 AN: 78256

European-Finnish (FIN) AF: 0.217 AC: 10981 AN: 50688

Middle Eastern (MID) AF: 0.208 AC: 850 AN: 4086

European-Non Finnish (NFE) AF: 0.285 AC: 308895 AN: 1083206

Other (OTH) AF: 0.272 AC: 15687 AN: 57688

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

African (AFR) AF: 0.135 AC: 5426 AN: 40274

American (AMR) AF: 0.286 AC: 4253 AN: 14848

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 996 AN: 3456

East Asian (EAS) AF: 0.353 AC: 1814 AN: 5132

South Asian (SAS) AF: 0.249 AC: 1149 AN: 4610

European-Finnish (FIN) AF: 0.217 AC: 2260 AN: 10404

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19116 AN: 67282

Other (OTH) AF: 0.261 AC: 534 AN: 2048

Alfa AF: 0.261 Hom.: 7507

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
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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