4-23820705-G-C

Variant names:

• chr4-23820705-G-C
• rs2932976
• NM_013261.5:c.877+3575C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013261.5(PPARGC1A):​c.877+3575C>G variant causes a intron 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPARGC1A NM_013261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013261.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.877+3575C>G		intron	N/A	NP_037393.1
	PPARGC1A	NM_001330751.2		c.892+3575C>G		intron	N/A	NP_001317680.1
	PPARGC1A	NM_001354825.2		c.892+3575C>G		intron	N/A	NP_001341754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.877+3575C>G		intron	N/A	ENSP00000264867.2
	PPARGC1A	ENST00000613098.4	TSL:1	c.496+3575C>G		intron	N/A	ENSP00000481498.1
	PPARGC1A	ENST00000506055.5	TSL:1	n.*92+3575C>G		intron	N/A	ENSP00000423075.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 196376 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 114860

African (AFR) AF: 0.00 AC: 0 AN: 4650

American (AMR) AF: 0.00 AC: 0 AN: 16098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7078

East Asian (EAS) AF: 0.00 AC: 0 AN: 5320

South Asian (SAS) AF: 0.00 AC: 0 AN: 41750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 100842

Other (OTH) AF: 0.00 AC: 0 AN: 9014

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7719

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		1.4

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

Other links and lift over

dbSNP: rs2932976; hg19: chr4-23822328;