rs1805192
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_138711.6(PPARG):c.28C>G(p.Pro10Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
PPARG
NM_138711.6 missense
NM_138711.6 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 4.22
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PPARG. . Gene score misZ 2.1192 (greater than the threshold 3.09). Trascript score misZ 3.0978 (greater than threshold 3.09). GenCC has associacion of gene with PPARG-related familial partial lipodystrophy, Berardinelli-Seip congenital lipodystrophy.
BP4
Computational evidence support a benign effect (MetaRNN=0.2985686).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPARG | NM_138711.6 | c.28C>G | p.Pro10Ala | missense_variant | 3/8 | ENST00000651735.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPARG | ENST00000651735.1 | c.28C>G | p.Pro10Ala | missense_variant | 3/8 | NM_138711.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: risk factor
Submissions summary: Other:4
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Body mass index, modifier of Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 01, 2007 | - - |
Obesity, modifier of Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 01, 2007 | - - |
Intimal medial thickness of internal carotid artery, modifier of Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 01, 2007 | - - |
Diabetes mellitus, noninsulin-dependent, modifier of Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.;.;.;.;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;.;.;.;.;D;.;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;.;.;.;L
MutationTaster
Benign
A;A;A;A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;.;.;D;N;N;D;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;.;.;.;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;.;.;.;T;D;D;T;D;D
Polyphen
0.35, 0.20
.;.;.;.;.;.;.;.;.;.;.;B;B
Vest4
MutPred
0.26
.;.;.;.;.;.;.;.;.;.;.;.;Loss of glycosylation at T41 (P = 0.048);
MVP
MPC
0.14
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at