dbSNP rs144211994: PPARD:p.Thr376Ala (chr6-35425879-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006238.5(PPARD):c.1126A>G(p.Thr376Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPARD
NM_006238.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.13

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]

PPARD links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20436373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARD	NM_006238.5 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 8 of 8	ENST00000360694.8	NP_006229.1	Q03181-1A0A024RCW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPARD	ENST00000360694.8 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 8 of 8	2	NM_006238.5	ENSP00000353916.3	Q03181-1
PPARD	ENST00000311565.4 link	c.1126A>G	p.Thr376Ala	missense_variant	Exon 9 of 9	5		ENSP00000310928.4	Q03181-1
PPARD	ENST00000448077.6 link	c.1009A>G	p.Thr337Ala	missense_variant	Exon 7 of 7	2		ENSP00000414372.2	Q03181-3
PPARD	ENST00000418635.6 link	c.832A>G	p.Thr278Ala	missense_variant	Exon 6 of 6	2		ENSP00000413314.2	Q03181-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

.;D;.;D

Eigen

Benign

0.062

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

T;T;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;.;L

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.087

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.039

.;B;.;B

Vest4

0.15

MutPred

0.44

.;Loss of catalytic residue at R379 (P = 0.4538);.;Loss of catalytic residue at R379 (P = 0.4538);

MVP

0.58

MPC

0.76

ClinPred

0.68

GERP RS

5.0

Varity_R

0.19

gMVP

0.061

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over