7-95589126-T-C

Position:

• chr7-95589126-T-C

Variant summary

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

The NM_002612.4(PDK4):​c.771+514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,112 control chromosomes in the GnomAD database, including 7,513 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 0.30 (7513 hom., cov: 32)
• Consequence: PDK4 NM_002612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDK4	NM_002612.4	c.771+514A>G		intron_variant		ENST00000005178.6	NP_002603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDK4	ENST00000005178.6	c.771+514A>G		intron_variant		1	NM_002612.4	ENSP00000005178.5

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45117 AN: 151994 Hom.: 7498 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45158 AN: 152112 Hom.: 7513 Cov.: 32 AF XY: 0.300 AC XY: 22338 AN XY: 74364

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.334

Alfa AF: 0.291 Hom.: 9076

Bravo AF: 0.304

Asia WGS AF: 0.580 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.75

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: rs12668651; hg19: chr7-95218438;