dbSNP rs10085637: PDK4:c.-208A>G (chr7-95596501-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002612.4(PDK4):c.-208A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 508,604 control chromosomes in the GnomAD database, including 38,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12980 hom., cov: 31)

Exomes 𝑓: 0.36 ( 25933 hom. )

Consequence

PDK4
NM_002612.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.950

Variant links:

Genes affected

PDK4 (HGNC:8812): (pyruvate dehydrogenase kinase 4) This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq, Jul 2008]

PDK4 links:

PDK4-AS1 (HGNC:55767): (PDK4 antisense RNA 1)

PDK4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK4	NM_002612.4 link	c.-208A>G		5_prime_UTR_variant	Exon 1 of 11	ENST00000005178.6	NP_002603.1	Q16654A4D1H4
PDK4-AS1	XR_001745287.3 link	n.-178T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK4	ENST00000005178.6 link	c.-208A>G		5_prime_UTR_variant	Exon 1 of 11	1	NM_002612.4	ENSP00000005178.5		Q16654

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60748

AN:

151406

Hom.:

12966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.520

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.418

GnomAD4 exome

AF:

0.363

AC:

129790

AN:

357080

Hom.:

25933

Cov.:

AF XY:

0.366

AC XY:

67949

AN XY:

185512

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.694

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.318

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.401

AC:

60801

AN:

151524

Hom.:

12980

Cov.:

AF XY:

0.402

AC XY:

29767

AN XY:

74030

show subpopulations

Gnomad4 AFR

AF:

0.520

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.324

Gnomad4 OTH

AF:

0.421

Alfa

AF:

0.348

Hom.:

9226

Bravo

AF:

0.412

Asia WGS

AF:

0.609

AC:

2115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.2

DANN

Benign

0.37

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over