chr6-35426036-C-T

Position:

chr6-35426036-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006238.5(PPARD):c.1283C>T(p.Ser428Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

PPARD
NM_006238.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.74

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049342483).

BP6

Variant 6-35426036-C-T is Benign according to our data. Variant chr6-35426036-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2348461.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPARD	NM_006238.5 linkuse as main transcript	c.1283C>T	p.Ser428Leu	missense_variant	8/8	ENST00000360694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPARD	ENST00000360694.8 linkuse as main transcript	c.1283C>T	p.Ser428Leu	missense_variant	8/8	2	NM_006238.5	P1	Q03181-1
PPARD	ENST00000311565.4 linkuse as main transcript	c.1283C>T	p.Ser428Leu	missense_variant	9/9	5		P1	Q03181-1
PPARD	ENST00000448077.6 linkuse as main transcript	c.1166C>T	p.Ser389Leu	missense_variant	7/7	2			Q03181-3
PPARD	ENST00000418635.6 linkuse as main transcript	c.989C>T	p.Ser330Leu	missense_variant	6/6	2			Q03181-4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

250992

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000145

AC:

AN:

151590

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74096

show subpopulations

Gnomad4 AFR

AF:

0.000461

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

.;D;.;D

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.85

T;D;T;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M;.;M

MutationTaster

Benign

0.95

D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.099

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.10

.;B;.;B

Vest4

0.087

MVP

0.43

MPC

0.67

ClinPred

0.034

GERP RS

0.88

Varity_R

0.18

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over