rs11531570

Positions:

• chr7-95584390-G-A
• chr7-95584390-G-C

Variant summary

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

The ENST00000005178.6(PDK4):​c.*1251C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,618 control chromosomes in the GnomAD database, including 13,603 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 0.42 (13603 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PDK4 ENST00000005178.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.89).
• 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.*1251C>T		3_prime_UTR_variant	11/11	ENST00000005178.6	NP_002603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDK4	ENST00000005178.6	c.*1251C>T		3_prime_UTR_variant	11/11	1	NM_002612.4	ENSP00000005178	P1
PDK4-AS1	ENST00000665332.1	n.37-28661G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63172 AN: 151492 Hom.: 13597 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.417 AC: 63207 AN: 151610 Hom.: 13603 Cov.: 32 AF XY: 0.421 AC XY: 31182 AN XY: 74062

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.464

Alfa AF: 0.418 Hom.: 22822

Bravo AF: 0.413

Asia WGS AF: 0.624 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.082
DANN	Benign	0.23

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: rs11531570; hg19: chr7-95213702;