Variant 5-149730381-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_133263.4(PPARGC1B):c.39G>T(p.Glu13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,423,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

PPARGC1B
NM_133263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

Variant links:

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]

PPARGC1B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14453235).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARGC1B	NM_133263.4 linkuse as main transcript	c.39G>T	p.Glu13Asp	missense_variant	1/12	ENST00000309241.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARGC1B	ENST00000309241.10 linkuse as main transcript	c.39G>T	p.Glu13Asp	missense_variant	1/12	1	NM_133263.4	P2	Q86YN6-1
PPARGC1B	ENST00000394320.7 linkuse as main transcript	c.39G>T	p.Glu13Asp	missense_variant	1/11	1		A2	Q86YN6-3
PPARGC1B	ENST00000360453.8 linkuse as main transcript	c.39G>T	p.Glu13Asp	missense_variant	1/11	1		A2	Q86YN6-5
PPARGC1B	ENST00000461780.1 linkuse as main transcript	n.79G>T		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1423576

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000456

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.39G>T (p.E13D) alteration is located in exon 1 (coding exon 1) of the PPARGC1B gene. This alteration results from a G to T substitution at nucleotide position 39, causing the glutamic acid (E) at amino acid position 13 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.072

.;.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.043

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.60

T;T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

0.61

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.069

Sift

Uncertain

0.022

D;D;D

Sift4G

Benign

0.39

T;T;T

Polyphen

0.15

B;B;B

Vest4

0.25

MutPred

0.35

Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.25

MPC

0.16

ClinPred

0.34

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.22

gMVP

0.11

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