rs1800571

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PP2PP3_Moderate

The NM_138711.6(PPARG):c.248C>A(p.Pro83Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PPARG
NM_138711.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 7.55

Publications

74 publications found

Variant links:

Genes affected

PPARG (HGNC:9236): (peroxisome proliferator activated receptor gamma) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

PPARG Gene-Disease associations (from GenCC):

PPARG-related familial partial lipodystrophy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
lipodystrophy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PPARG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PP2

Missense variant in the PPARG gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: 2.1192 (below the threshold of 3.09). Trascript score misZ: 3.0978 (above the threshold of 3.09). GenCC associations: The gene is linked to PPARG-related familial partial lipodystrophy, Berardinelli-Seip congenital lipodystrophy.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.844

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138711.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPARG	NM_138711.6	MANE Select	c.248C>A	p.Pro83Gln	missense	Exon 4 of 8	NP_619725.3	E9PFV2
PPARG	NM_015869.5		c.338C>A	p.Pro113Gln	missense	Exon 3 of 7	NP_056953.2
PPARG	NM_001354666.3		c.248C>A	p.Pro83Gln	missense	Exon 4 of 8	NP_001341595.2	E9PFV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPARG	ENST00000651735.1	MANE Select	c.248C>A	p.Pro83Gln	missense	Exon 4 of 8	ENSP00000498313.1	E9PFV2
PPARG	ENST00000287820.10	TSL:1	c.338C>A	p.Pro113Gln	missense	Exon 3 of 7	ENSP00000287820.6	P37231-1
PPARG	ENST00000397010.7	TSL:1	c.248C>A	p.Pro83Gln	missense	Exon 4 of 8	ENSP00000380205.3	E9PFV2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461054

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111634

Other (OTH)

AF:

0.0000166

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Morbid obesity (1)

not provided (1)

Type 2 diabetes mellitus;C1720861:PPARG-related familial partial lipodystrophy;C1836302:CAROTID INTIMAL MEDIAL THICKNESS 1;C4054476:Inherited obesity (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.84

MetaSVM

Pathogenic

0.90

MutationAssessor

Uncertain

2.4

PhyloP100

7.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.84

MutPred

0.59

Gain of glycosylation at Y116 (P = 0.0123)

MVP

0.94

MPC

0.55

ClinPred

0.98

GERP RS

5.6

Varity_R

0.27

gMVP

0.65

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

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

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