chr3-12392682-CA-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_138711.6(PPARG):c.466delA(p.Ser156ValfsTer47) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PPARG
NM_138711.6 frameshift
NM_138711.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.31
Publications
5 publications found
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 lipodystrophyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
- lipodystrophyInheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
- Berardinelli-Seip congenital lipodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-12392682-CA-C is Pathogenic according to our data. Variant chr3-12392682-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 8132.Status of the report is no_assertion_criteria_provided, 0 stars.
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPARG | MANE Select | c.466delA | p.Ser156ValfsTer47 | frameshift | Exon 5 of 8 | NP_619725.3 | E9PFV2 | ||
| PPARG | c.556delA | p.Ser186ValfsTer47 | frameshift | Exon 4 of 7 | NP_056953.2 | ||||
| PPARG | c.466delA | p.Ser156ValfsTer47 | frameshift | Exon 5 of 8 | NP_001341595.2 | E9PFV2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PPARG | MANE Select | c.466delA | p.Ser156ValfsTer47 | frameshift | Exon 5 of 8 | ENSP00000498313.1 | E9PFV2 | ||
| PPARG | TSL:1 | c.556delA | p.Ser186ValfsTer47 | frameshift | Exon 4 of 7 | ENSP00000287820.6 | P37231-1 | ||
| PPARG | TSL:1 | c.466delA | p.Ser156ValfsTer47 | frameshift | Exon 5 of 8 | ENSP00000380205.3 | E9PFV2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251006 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251006
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461568Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727074 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461568
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727074
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33460
American (AMR)
AF:
AC:
0
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
0
AN:
39668
South Asian (SAS)
AF:
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
AC:
1
AN:
53402
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111814
Other (OTH)
AF:
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
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0.00
0.20
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0.60
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0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Carcinoma of colon (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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