rs2076167

Positions:

• chr6-35424010-C-G
• chr6-35424010-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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]

ACMG classification

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
PPARD	NM_006238.5	c.489C>G	p.Asn163Lys	missense_variant	6/8	ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8	c.489C>G	p.Asn163Lys	missense_variant	6/8	2	NM_006238.5	P1

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

Other links and lift over

dbSNP: rs2076167; hg19: chr6-35391787;