4-23814039-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013261.5(PPARGC1A):​c.1444G>C​(p.Gly482Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G482S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PPARGC1A
NM_013261.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21
Variant links:
Genes affected
PPARGC1A (HGNC:9237): (PPARG coactivator 1 alpha) The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06643617).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPARGC1ANM_013261.5 linkc.1444G>C p.Gly482Arg missense_variant Exon 8 of 13 ENST00000264867.7 NP_037393.1 Q9UBK2-1A0A024R9Q9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPARGC1AENST00000264867.7 linkc.1444G>C p.Gly482Arg missense_variant Exon 8 of 13 1 NM_013261.5 ENSP00000264867.2 Q9UBK2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
55
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
17
DANN
Benign
0.86
DEOGEN2
Benign
0.21
T;.
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.45
N;.
REVEL
Benign
0.059
Sift
Benign
0.46
T;.
Sift4G
Benign
0.17
T;T
Polyphen
0.041
B;.
Vest4
0.10
MutPred
0.17
Gain of solvent accessibility (P = 0.0128);.;
MVP
0.23
MPC
0.26
ClinPred
0.17
T
GERP RS
6.0
Varity_R
0.038
gMVP
0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-23815662; API