7-95586935-A-G

Position:

• chr7-95586935-A-G

Variant summary

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

The NM_002612.4(PDK4):​c.1095+75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 801,930 control chromosomes in the GnomAD database, including 67,396 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 0.43 (15031 hom., cov: 32)
  • Exomes 𝑓: 0.39 (52365 hom.)
• Consequence: PDK4 NM_002612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDK4	NM_002612.4	c.1095+75T>C		intron_variant		ENST00000005178.6	NP_002603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDK4	ENST00000005178.6	c.1095+75T>C		intron_variant		1	NM_002612.4	ENSP00000005178.5

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65624 AN: 151932 Hom.: 15008 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.385 AC: 250235 AN: 649880 Hom.: 52365 Cov.: 9 AF XY: 0.387 AC XY: 133723 AN XY: 345724

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.432 AC: 65691 AN: 152050 Hom.: 15031 Cov.: 32 AF XY: 0.432 AC XY: 32097 AN XY: 74328

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.465

Alfa AF: 0.385 Hom.: 23628

Bravo AF: 0.443

Asia WGS AF: 0.632 AC: 2196 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.48

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: rs10247649; hg19: chr7-95216247; COSMIC: COSV50012679; COSMIC: COSV50012679;