rs32588

Variant names:

• chr5-149820480-T-A
• NM_133263.4:c.126T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-149820480-T-A
• chr5-149820480-T-C
• chr5-149820480-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_133263.4(PPARGC1B):​c.126T>A​(p.Leu42Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPARGC1B NM_133263.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARGC1B	NM_133263.4	c.126T>A	p.Leu42Leu	synonymous_variant	Exon 2 of 12	ENST00000309241.10	NP_573570.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARGC1B	ENST00000309241.10	c.126T>A	p.Leu42Leu	synonymous_variant	Exon 2 of 12	1	NM_133263.4	ENSP00000312649.5
PPARGC1B	ENST00000394320.7	c.126T>A	p.Leu42Leu	synonymous_variant	Exon 2 of 11	1		ENSP00000377855.3
PPARGC1B	ENST00000360453.8	c.126T>A	p.Leu42Leu	synonymous_variant	Exon 2 of 11	1		ENSP00000353638.4
PPARGC1B	ENST00000403750.5	c.51T>A	p.Leu17Leu	synonymous_variant	Exon 2 of 11	2		ENSP00000384403.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr5-149200043;