3-12434058-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_138711.6(PPARG):c.1341C>T(p.His447=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,614,040 control chromosomes in the GnomAD database, including 13,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 1153 hom., cov: 32)
Exomes 𝑓: 0.13 ( 12668 hom. )
Consequence
PPARG
NM_138711.6 synonymous
NM_138711.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.333
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 3-12434058-C-T is Benign according to our data. Variant chr3-12434058-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 8139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=-0.333 with no splicing effect.
BA1
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GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPARG | NM_138711.6 | c.1341C>T | p.His447= | synonymous_variant | 8/8 | ENST00000651735.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPARG | ENST00000651735.1 | c.1341C>T | p.His447= | synonymous_variant | 8/8 | NM_138711.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.114 AC: 17378AN: 152060Hom.: 1149 Cov.: 32
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GnomAD3 exomes AF: 0.134 AC: 33702AN: 251322Hom.: 2568 AF XY: 0.136 AC XY: 18405AN XY: 135826
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GnomAD4 exome AF: 0.128 AC: 187677AN: 1461862Hom.: 12668 Cov.: 32 AF XY: 0.129 AC XY: 93871AN XY: 727234
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GnomAD4 genome ? AF: 0.114 AC: 17390AN: 152178Hom.: 1153 Cov.: 32 AF XY: 0.116 AC XY: 8636AN XY: 74384
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2019 | This variant is associated with the following publications: (PMID: 18992148, 17141766, 22575725, 21795447, 10851250, 21833536, 9467001) - |
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Dec 01, 2003 | - - |
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Glioma susceptibility 1 Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jun 01, 2000 | - - |
Obesity Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Diabetes Mellitus, Noninsulin-Dependent, with Acanthosis Nigricans and Hypertension Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
PPARG-related familial partial lipodystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at