Genetic Variant PLIN3:c.960+47G>A (chr19-4844621-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.444

Publications

14 publications found

Variant links:

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]

PLIN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005817.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLIN3	NM_005817.5	MANE Select	c.960+47G>A	intron	N/A	NP_005808.3
PLIN3	NM_001164189.2		c.960+47G>A	intron	N/A	NP_001157661.1	O60664-3
PLIN3	NM_001164194.2		c.924+47G>A	intron	N/A	NP_001157666.1	O60664-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLIN3	ENST00000221957.9	TSL:1 MANE Select	c.960+47G>A	intron	N/A	ENSP00000221957.3	O60664-1
PLIN3	ENST00000585479.5	TSL:1	c.960+47G>A	intron	N/A	ENSP00000465596.1	O60664-3
PLIN3	ENST00000884464.1		c.960+47G>A	intron	N/A	ENSP00000554523.1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

35761

AN:

149122

Hom.:

4579

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.277

AC XY:

192107

AN XY:

693840

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12508

25016

37524

50032

62540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10472

20944

31416

41888

52360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.240

AC:

35760

AN:

149240

Hom.:

4579

Cov.:

AF XY:

0.238

AC XY:

17304

AN XY:

72754

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.284

AC:

19116

AN:

67282

Other (OTH)

AF:

0.261

AC:

534

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1379

2757

4136

5514

6893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

(source)

DANN

Benign

0.77

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over