Variant 4-23795928-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_013261.5(PPARGC1A):c.2294-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,598,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PPARGC1A
NM_013261.5 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

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]

PPARGC1A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 4-23795928-G-GA is Benign according to our data. Variant chr4-23795928-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 3341509.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPARGC1A	NM_013261.5 link	c.2294-4dupT		splice_region_variant, intron_variant		ENST00000264867.7	NP_037393.1	Q9UBK2-1A0A024R9Q9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PPARGC1A	ENST00000264867.7 link	c.2294-4_2294-3insT	splice_region_variant, intron_variant	1	NM_013261.5	ENSP00000264867.2	Q9UBK2-1
PPARGC1A	ENST00000613098.4 link	c.1913-4_1913-3insT	splice_region_variant, intron_variant	1		ENSP00000481498.1	Q9UBK2-9
PPARGC1A	ENST00000506055.5 link	n.1509-4_1509-3insT	splice_region_variant, intron_variant	1		ENSP00000423075.1	Q9UBK2-2
PPARGC1A	ENST00000509702.5 link	n.2334-4_2334-3insT	splice_region_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.000371

AC:

AN:

151052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00346

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000367

AC:

AN:

237110

Hom.:

AF XY:

0.000327

AC XY:

AN XY:

128360

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.000192

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.000177

Gnomad SAS exome

AF:

0.000283

Gnomad FIN exome

AF:

0.00253

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

237

AN:

1447082

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

117

AN XY:

720176

show subpopulations

Gnomad4 AFR exome

AF:

0.000308

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.0000771

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.000237

Gnomad4 FIN exome

AF:

0.00261

Gnomad4 NFE exome

AF:

0.0000371

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000377

AC:

AN:

151168

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

AN XY:

73770

show subpopulations

Gnomad4 AFR

AF:

0.000340

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00346

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

PPARGC1A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over