chr5-149730358-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133263.4(PPARGC1B):ā€‹c.16T>Cā€‹(p.Cys6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PPARGC1B
NM_133263.4 missense

Scores

5
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.928
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPARGC1BNM_133263.4 linkuse as main transcriptc.16T>C p.Cys6Arg missense_variant 1/12 ENST00000309241.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPARGC1BENST00000309241.10 linkuse as main transcriptc.16T>C p.Cys6Arg missense_variant 1/121 NM_133263.4 P2Q86YN6-1
PPARGC1BENST00000394320.7 linkuse as main transcriptc.16T>C p.Cys6Arg missense_variant 1/111 A2Q86YN6-3
PPARGC1BENST00000360453.8 linkuse as main transcriptc.16T>C p.Cys6Arg missense_variant 1/111 A2Q86YN6-5
PPARGC1BENST00000461780.1 linkuse as main transcriptn.56T>C non_coding_transcript_exon_variant 1/44

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1415374
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
701804
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJun 28, 2023The c.16T>C (p.C6R) alteration is located in exon 1 (coding exon 1) of the PPARGC1B gene. This alteration results from a T to C substitution at nucleotide position 16, causing the cysteine (C) at amino acid position 6 to be replaced by an arginine (R). 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
Pathogenic
0.92
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Benign
0.41
.;.;T
Eigen
Benign
0.13
Eigen_PC
Benign
0.16
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.59
T;T;T
M_CAP
Pathogenic
0.57
D
MetaRNN
Uncertain
0.44
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Benign
0.21
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.91
P;B;P
Vest4
0.63
MutPred
0.55
Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);
MVP
0.12
MPC
0.30
ClinPred
0.94
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.89
gMVP
0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149109921; API