Genetic Variant NM_002666.5:c.1306T>A (chr15-89665846-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_002666.5(PLIN1):c.1306T>A(p.Ser436Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000988 in 1,315,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity PLIN1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.006991029).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLIN1	NM_002666.5 link	c.1306T>A	p.Ser436Thr	missense_variant	Exon 9 of 9	ENST00000300055.10	NP_002657.3	O60240
PLIN1	NM_001145311.2 link	c.1306T>A	p.Ser436Thr	missense_variant	Exon 9 of 9		NP_001138783.1	O60240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLIN1	ENST00000300055.10 link	c.1306T>A	p.Ser436Thr	missense_variant	Exon 9 of 9	1	NM_002666.5	ENSP00000300055.5	O60240
PLIN1	ENST00000430628.2 link	c.1306T>A	p.Ser436Thr	missense_variant	Exon 9 of 9	5		ENSP00000402167.2	O60240
PLIN1	ENST00000560330.1 link	c.124-905T>A		intron_variant	Intron 2 of 2	5		ENSP00000453426.1	H0YM16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

93302

Hom.:

AF XY:

0.0000188

AC XY:

AN XY:

53096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

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:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000988

AC:

AN:

1315824

Hom.:

Cov.:

AF XY:

0.0000108

AC XY:

AN XY:

646628

show subpopulations

Gnomad4 AFR exome

AF:

0.000147

Gnomad4 AMR exome

AF:

0.0000347

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000338

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000383

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000959

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.42

.;T

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.096

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.98

D;D

Vest4

0.13

MutPred

0.16

Loss of glycosylation at S436 (P = 0.0613);Loss of glycosylation at S436 (P = 0.0613);

MVP

0.030

MPC

1.1

ClinPred

0.054

GERP RS

2.7

Varity_R

0.092

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over