GeneBe

rs2076167

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006238.5(PPARD):​c.489C>G​(p.Asn163Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PPARD
NM_006238.5 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81

Publications

54 publications found
Variant links:
Genes affected
PPARD (HGNC:9235): (peroxisome proliferator activated receptor delta) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. The encoded protein is thought to function as an integrator of transcriptional repression and nuclear receptor signaling. It may inhibit the ligand-induced transcriptional activity of peroxisome proliferator activated receptors alpha and gamma, though evidence for this effect is inconsistent. Expression of this gene in colorectal cancer cells may be variable but is typically relatively low. Knockout studies in mice suggested a role for this protein in myelination of the corpus callosum, lipid metabolism, differentiation, and epidermal cell proliferation. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027283728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006238.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PPARD
NM_006238.5
MANE Select
c.489C>Gp.Asn163Lys
missense
Exon 6 of 8NP_006229.1Q03181-1
PPARD
NM_001171818.2
c.489C>Gp.Asn163Lys
missense
Exon 7 of 9NP_001165289.1Q03181-1
PPARD
NM_001171819.2
c.372C>Gp.Asn124Lys
missense
Exon 5 of 7NP_001165290.1Q03181-3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PPARD
ENST00000360694.8
TSL:2 MANE Select
c.489C>Gp.Asn163Lys
missense
Exon 6 of 8ENSP00000353916.3Q03181-1
PPARD
ENST00000311565.4
TSL:5
c.489C>Gp.Asn163Lys
missense
Exon 7 of 9ENSP00000310928.4Q03181-1
PPARD
ENST00000875334.1
c.489C>Gp.Asn163Lys
missense
Exon 5 of 7ENSP00000545393.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
68
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
132326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
0.0050
DANN
Benign
0.70
DEOGEN2
Benign
0.37
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.027
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.0
N
PhyloP100
-2.8
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.12
N
REVEL
Benign
0.16
Sift
Benign
0.68
T
Sift4G
Benign
0.93
T
Polyphen
0.086
B
Vest4
0.12
MutPred
0.42
Gain of ubiquitination at N163 (P = 0.0082)
MVP
0.53
MPC
0.88
ClinPred
0.049
T
GERP RS
-4.8
Varity_R
0.029
gMVP
0.24
Mutation Taster
=77/23
polymorphism

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

Other links and lift over

dbSNP: rs2076167; hg19: chr6-35391787; API