rs2076167

Variant summary

Our verdict is Likely benign. Variant got -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. 16/21 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

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81
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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPARDNM_006238.5 linkuse as main transcriptc.489C>G p.Asn163Lys missense_variant 6/8 ENST00000360694.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPARDENST00000360694.8 linkuse as main transcriptc.489C>G p.Asn163Lys missense_variant 6/82 NM_006238.5 P1Q03181-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
68
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.82
T;T;T;T;.
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.027
T;T;T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.0
.;N;.;N;N
MutationTaster
Benign
1.0
P;P;P;P;P;P;P
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.12
N;N;N;N;N
REVEL
Benign
0.16
Sift
Benign
0.68
T;T;T;T;T
Sift4G
Benign
0.93
T;T;T;T;T
Polyphen
0.086
.;B;.;.;B
Vest4
0.12
MutPred
0.42
.;Gain of ubiquitination at N163 (P = 0.0082);.;Gain of ubiquitination at N163 (P = 0.0082);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

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.

Other links and lift over

dbSNP: rs2076167; hg19: chr6-35391787; API