Genetic Variant PPARGC1A:p.His610Pro (chr4-23813090-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013261.5(PPARGC1A):c.1829A>C(p.His610Pro) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PPARGC1A
NM_013261.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Publications

0 publications found

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 was made for transcript

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 (MetaRNN=0.11268145).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPARGC1A	NM_013261.5	MANE Select	c.1829A>C	p.His610Pro	missense	Exon 9 of 13	NP_037393.1	Q9UBK2-1
PPARGC1A	NM_001330751.2		c.1844A>C	p.His615Pro	missense	Exon 11 of 15	NP_001317680.1	Q9UBK2-3
PPARGC1A	NM_001354825.2		c.1844A>C	p.His615Pro	missense	Exon 10 of 14	NP_001341754.1	Q9UBK2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPARGC1A	ENST00000264867.7	TSL:1 MANE Select	c.1829A>C	p.His610Pro	missense	Exon 9 of 13	ENSP00000264867.2	Q9UBK2-1
PPARGC1A	ENST00000613098.4	TSL:1	c.1448A>C	p.His483Pro	missense	Exon 8 of 12	ENSP00000481498.1	Q9UBK2-9
PPARGC1A	ENST00000506055.5	TSL:1	n.*1044A>C		non_coding_transcript_exon	Exon 9 of 13	ENSP00000423075.1	Q9UBK2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.22

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

2.1

PrimateAI

Benign

0.44

PROVEAN

Benign

0.69

REVEL

Benign

0.055

Sift

Benign

0.25

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.38

MutPred

0.24

Gain of loop (P = 0.0312)

MVP

0.28

MPC

0.34

ClinPred

0.39

GERP RS

4.5

Varity_R

0.17

gMVP

0.32

Mutation Taster

=73/27

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over