NM_013261.5:c.1926C>T

Variant names:

• chr4-23812840-G-A
• rs200822395
• NM_013261.5:c.1926C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_013261.5(PPARGC1A):​c.1926C>T​(p.His642His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: PPARGC1A NM_013261.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.349
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 4-23812840-G-A is Benign according to our data. Variant chr4-23812840-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3350394.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.349 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 25 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	NM_013261.5	MANE Select	c.1926C>T	p.His642His	synonymous	Exon 10 of 13	NP_037393.1	Q9UBK2-1
	PPARGC1A	NM_001330751.2		c.1941C>T	p.His647His	synonymous	Exon 12 of 15	NP_001317680.1	Q9UBK2-3
	PPARGC1A	NM_001354825.2		c.1941C>T	p.His647His	synonymous	Exon 11 of 14	NP_001341754.1	Q9UBK2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.1926C>T	p.His642His	synonymous	Exon 10 of 13	ENSP00000264867.2	Q9UBK2-1
	PPARGC1A	ENST00000613098.4	TSL:1	c.1545C>T	p.His515His	synonymous	Exon 9 of 12	ENSP00000481498.1	Q9UBK2-9
	PPARGC1A	ENST00000506055.5	TSL:1	n.*1141C>T		non_coding_transcript_exon	Exon 10 of 13	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250180 AF XY: 0.0000444

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461744 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111950

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPARGC1A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.8
DANN	Benign	0.63
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200822395; hg19: chr4-23814463; COSMIC: COSV53531689; COSMIC: COSV53531689;