5-149832947-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_133263.4(PPARGC1B):c.874C>G(p.Arg292Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,460,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R292S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PPARGC1B NM_133263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1B	NM_133263.4	c.874C>G	p.Arg292Gly	missense_variant	5/12	ENST00000309241.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.874C>G	p.Arg292Gly	missense_variant	5/12	1	NM_133263.4	P2
PPARGC1B	ENST00000394320.7	c.874C>G	p.Arg292Gly	missense_variant	5/11	1		A2
PPARGC1B	ENST00000360453.8	c.757C>G	p.Arg253Gly	missense_variant	4/11	1		A2
PPARGC1B	ENST00000403750.5	c.682C>G	p.Arg228Gly	missense_variant	4/11	2		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248750 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134986

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1460938 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000272 Hom.: 426

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
Cadd	Uncertain	25
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.0030	P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.67
MVP		0.39
MPC		0.75
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs11959820; hg19: chr5-149212510;