NM_002666.5:c.814G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002666.5(PLIN1):c.814G>A(p.Val272Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,564,906 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 10 hom. )

Consequence

PLIN1
NM_002666.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.59

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

PLIN1-related familial partial lipodystrophy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp, Ambry Genetics

PLIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008209467).

BP6

Variant 15-89667751-C-T is Benign according to our data. Variant chr15-89667751-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 393437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 126 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN1	NM_002666.5	MANE Select	c.814G>A	p.Val272Met	missense	Exon 7 of 9	NP_002657.3	O60240
	PLIN1	NM_001145311.2		c.814G>A	p.Val272Met	missense	Exon 7 of 9	NP_001138783.1	O60240

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLIN1	ENST00000300055.10	TSL:1 MANE Select	c.814G>A	p.Val272Met	missense	Exon 7 of 9	ENSP00000300055.5	O60240
PLIN1	ENST00000896664.1		c.922G>A	p.Val308Met	missense	Exon 7 of 9	ENSP00000566723.1
PLIN1	ENST00000896666.1		c.844G>A	p.Val282Met	missense	Exon 7 of 9	ENSP00000566725.1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.0314

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:

0.000955

GnomAD2 exomes

AF:

0.00177

AC:

303

AN:

170880

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000354

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000524

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.000680

AC:

960

AN:

1412668

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

483

AN XY:

697878

show subpopulations

African (AFR)

AF:

0.0000306

AC:

AN:

32636

American (AMR)

AF:

0.000247

AC:

AN:

36390

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

664

AN:

25246

East Asian (EAS)

AF:

0.00

AC:

AN:

37492

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.000148

AC:

161

AN:

1086742

Other (OTH)

AF:

0.00211

AC:

124

AN:

58660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000828

AC:

126

AN:

152238

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41454

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68050

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.00142

Hom.:

Bravo

AF:

0.000971

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00152

AC:

ExAC

AF:

0.000877

AC:

102

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Monogenic diabetes (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

M_CAP

Benign

0.019

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

2.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.53

REVEL

Benign

0.18

Sift

Uncertain

0.019

Sift4G

Benign

0.095

Polyphen

0.99

Vest4

0.37

MVP

0.19

MPC

0.17

ClinPred

0.063

GERP RS

4.8

PromoterAI

0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.94

Varity_R

0.13

gMVP

0.33

Mutation Taster

=89/11

polymorphism

(source)

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

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