Variant 15-89665720-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_002666.5(PLIN1):c.1432G>A(p.Ala478Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,306,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.761

Variant links:

Genes affected

PLIN1 (HGNC:9076): (perilipin 1) The protein encoded by this gene coats lipid storage droplets in adipocytes, thereby protecting them until they can be broken down by hormone-sensitive lipase. The encoded protein is the major cAMP-dependent protein kinase substrate in adipocytes and, when unphosphorylated, may play a role in the inhibition of lipolysis. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Feb 2009]

PLIN1 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=0.04956919).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLIN1	NM_002666.5 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant	9/9	ENST00000300055.10
PLIN1	NM_001145311.2 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLIN1	ENST00000300055.10 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant	9/9	1	NM_002666.5	P1
PLIN1	ENST00000430628.2 linkuse as main transcript	c.1432G>A	p.Ala478Thr	missense_variant	9/9	5		P1
PLIN1	ENST00000560330.1 linkuse as main transcript	c.124-779G>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

80454

Hom.:

AF XY:

0.00

AC XY:

AN XY:

46142

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000342

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1306744

Hom.:

Cov.:

AF XY:

0.0000109

AC XY:

AN XY:

643884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Feb 27, 2023

The c.1432G>A (p.A478T) alteration is located in exon 9 (coding exon 8) of the PLIN1 gene. This alteration results from a G to A substitution at nucleotide position 1432, causing the alanine (A) at amino acid position 478 to be replaced by a threonine (T). 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

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.79

DANN

Benign

0.95

DEOGEN2

Benign

0.096

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.044

M_CAP

Benign

0.023

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.014

Sift

Benign

0.32

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.059

B;B

Vest4

0.067

MutPred

0.12

Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);

MVP

0.014

MPC

1.2

ClinPred

0.10

GERP RS

-4.0

Varity_R

0.058

gMVP

0.098

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.

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