Variant 19-4523874-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013706.3(PLIN5):c.1046G>A(p.Gly349Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,522,790 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 3 hom. )

Consequence

PLIN5
NM_001013706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.489

Variant links:

Genes affected

PLIN5 (HGNC:33196): (perilipin 5) Predicted to enable identical protein binding activity and lipase binding activity. Predicted to be involved in several processes, including negative regulation of peroxisome proliferator activated receptor signaling pathway; regulation of lipase activity; and regulation of lipid metabolic process. Located in intracellular membrane-bounded organelle and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

PLIN5 links:

PLIN5 (HGNC:):

PLIN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04117456).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN5	NM_001013706.3 linkuse as main transcript	c.1046G>A	p.Gly349Asp	missense_variant	8/8	ENST00000381848.7	NP_001013728.2	Q00G26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLIN5	ENST00000381848.7 linkuse as main transcript	c.1046G>A	p.Gly349Asp	missense_variant	8/8	1	NM_001013706.3	ENSP00000371272.2		Q00G26
PLIN5	ENST00000589728.1 linkuse as main transcript	n.*35G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000146

AC:

AN:

123630

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

69792

show subpopulations

Gnomad AFR exome

AF:

0.000574

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000842

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1370482

Hom.:

Cov.:

AF XY:

0.0000694

AC XY:

AN XY:

677482

show subpopulations

Gnomad4 AFR exome

AF:

0.000413

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000781

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000701

GnomAD4 genome

AF:

0.000112

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000849

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1046G>A (p.G349D) alteration is located in exon 8 (coding exon 7) of the PLIN5 gene. This alteration results from a G to A substitution at nucleotide position 1046, causing the glycine (G) at amino acid position 349 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.57

M_CAP

Benign

0.068

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.060

REVEL

Benign

0.12

Sift

Benign

0.17

Sift4G

Benign

0.67

Polyphen

0.041

Vest4

0.25

MutPred

0.58

Loss of catalytic residue at G349 (P = 0.004);

MVP

0.48

MPC

0.39

ClinPred

0.036

GERP RS

3.8

Varity_R

0.11

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over