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GeneBe

19-4852062-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005817.5(PLIN3):c.588G>A(p.Ser196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000804 in 1,613,948 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 10 hom. )

Consequence

PLIN3
NM_005817.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.78
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-4852062-C-T is Benign according to our data. Variant chr19-4852062-C-T is described in ClinVar as [Benign]. Clinvar id is 723711.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.78 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLIN3NM_005817.5 linkuse as main transcriptc.588G>A p.Ser196= synonymous_variant 5/8 ENST00000221957.9
PLIN3NM_001164189.2 linkuse as main transcriptc.588G>A p.Ser196= synonymous_variant 5/8
PLIN3NM_001164194.2 linkuse as main transcriptc.552G>A p.Ser184= synonymous_variant 5/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLIN3ENST00000221957.9 linkuse as main transcriptc.588G>A p.Ser196= synonymous_variant 5/81 NM_005817.5 P3O60664-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00389
AC:
592
AN:
152108
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0135
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
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:
0.000176
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00102
AC:
256
AN:
250746
Hom.:
5
AF XY:
0.000767
AC XY:
104
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.0137
Gnomad AMR exome
AF:
0.000492
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000481
AC:
703
AN:
1461722
Hom.:
10
Cov.:
31
AF XY:
0.000413
AC XY:
300
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.0137
Gnomad4 AMR exome
AF:
0.000604
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000128
Gnomad4 OTH exome
AF:
0.00104
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00391
AC:
595
AN:
152226
Hom.:
6
Cov.:
32
AF XY:
0.00383
AC XY:
285
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0135
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00212
Hom.:
2
Bravo
AF:
0.00430
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
1.1
Dann
Benign
0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149440810; hg19: chr19-4852074; COSMIC: COSV55737170; COSMIC: COSV55737170; API