chr5-149826745-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_133263.4(PPARGC1B):c.325G>A(p.Gly109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,613,906 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 2 hom. )
Consequence
PPARGC1B
NM_133263.4 missense
NM_133263.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 3.04
Genes affected
PPARGC1B (HGNC:30022): (PPARG coactivator 1 beta) The protein encoded by this gene stimulates the activity of several transcription factors and nuclear receptors, including estrogen receptor alpha, nuclear respiratory factor 1, and glucocorticoid receptor. The encoded protein may be involved in fat oxidation, non-oxidative glucose metabolism, and the regulation of energy expenditure. This protein is downregulated in prediabetic and type 2 diabetes mellitus patients. Certain allelic variations in this gene increase the risk of the development of obesity. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00907135).
BS2
?
High AC in GnomAd at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPARGC1B | NM_133263.4 | c.325G>A | p.Gly109Ser | missense_variant | 3/12 | ENST00000309241.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPARGC1B | ENST00000309241.10 | c.325G>A | p.Gly109Ser | missense_variant | 3/12 | 1 | NM_133263.4 | P2 | |
PPARGC1B | ENST00000394320.7 | c.325G>A | p.Gly109Ser | missense_variant | 3/11 | 1 | A2 | ||
PPARGC1B | ENST00000360453.8 | c.325G>A | p.Gly109Ser | missense_variant | 3/11 | 1 | A2 | ||
PPARGC1B | ENST00000403750.5 | c.250G>A | p.Gly84Ser | missense_variant | 3/11 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152068Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000302 AC: 76AN: 251410Hom.: 1 AF XY: 0.000287 AC XY: 39AN XY: 135892
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GnomAD4 exome AF: 0.000140 AC: 204AN: 1461838Hom.: 2 Cov.: 32 AF XY: 0.000142 AC XY: 103AN XY: 727228
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GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152068Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74282
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2021 | The c.325G>A (p.G109S) alteration is located in exon 3 (coding exon 3) of the PPARGC1B gene. This alteration results from a G to A substitution at nucleotide position 325, causing the glycine (G) at amino acid position 109 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;P;B;.
Vest4
MVP
MPC
0.63
ClinPred
T
GERP RS
Varity_R
gMVP
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