rs10085637

Positions:

• chr7-95596501-T-C
• chr7-95596501-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950

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

ACMG classification

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/exons	MANE	UniProt
PDK4	NM_002612.4	c.-208A>G		5_prime_UTR_variant	1/11	ENST00000005178.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDK4	ENST00000005178.6	c.-208A>G		5_prime_UTR_variant	1/11	1	NM_002612.4	P1
PDK4-AS1	ENST00000665332.1	n.37-16550T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60748 AN: 151406 Hom.: 12966 Cov.: 31

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.: 5 AF XY: 0.366 AC XY: 67949 AN XY: 185512

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.: 31 AF XY: 0.402 AC XY: 29767 AN XY: 74030

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

Other links and lift over

dbSNP: rs10085637; hg19: chr7-95225813; COSMIC: COSV50011471;