Genetic Variant NM_005817.5:c.829A>G (chr19-4847696-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005817.5(PLIN3):c.829A>G(p.Ser277Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,597,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PLIN3
NM_005817.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.955

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.211804).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN3	NM_005817.5	MANE Select	c.829A>G	p.Ser277Gly	missense	Exon 6 of 8	NP_005808.3
PLIN3	NM_001164189.2		c.829A>G	p.Ser277Gly	missense	Exon 6 of 8	NP_001157661.1	O60664-3
PLIN3	NM_001164194.2		c.793A>G	p.Ser265Gly	missense	Exon 6 of 8	NP_001157666.1	O60664-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN3	ENST00000221957.9	TSL:1 MANE Select	c.829A>G	p.Ser277Gly	missense	Exon 6 of 8	ENSP00000221957.3	O60664-1
PLIN3	ENST00000585479.5	TSL:1	c.829A>G	p.Ser277Gly	missense	Exon 6 of 8	ENSP00000465596.1	O60664-3
PLIN3	ENST00000884464.1		c.829A>G	p.Ser277Gly	missense	Exon 6 of 8	ENSP00000554523.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225162

AF XY:

0.00000818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1445702

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

718194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33082

American (AMR)

AF:

0.00

AC:

AN:

42200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25718

East Asian (EAS)

AF:

0.00

AC:

AN:

39034

South Asian (SAS)

AF:

0.00

AC:

AN:

84162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4936

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1104774

Other (OTH)

AF:

0.00

AC:

AN:

59706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.070

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.50

M_CAP

Benign

0.027

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PhyloP100

0.95

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

REVEL

Benign

0.051

Sift

Benign

0.37

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.13

MutPred

0.36

Loss of disorder (P = 0.0972)

MVP

0.11

MPC

0.091

ClinPred

0.051

GERP RS

0.70

Varity_R

0.031

gMVP

0.044

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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