7-95596501-T-C

Variant names:

• chr7-95596501-T-C
• rs10085637
• NM_002612.4:c.-208A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002612.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	NM_002612.4	MANE Select	c.-208A>G		5_prime_UTR	Exon 1 of 11	NP_002603.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	ENST00000005178.6	TSL:1 MANE Select	c.-208A>G		5_prime_UTR	Exon 1 of 11	ENSP00000005178.5
	PDK4	ENST00000886050.1		c.-208A>G		5_prime_UTR	Exon 1 of 11	ENSP00000556109.1
	PDK4	ENST00000886051.1		c.-208A>G		5_prime_UTR	Exon 1 of 11	ENSP00000556110.1

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

African (AFR) AF: 0.507 AC: 3843 AN: 7578

American (AMR) AF: 0.349 AC: 2705 AN: 7752

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 4908 AN: 11250

East Asian (EAS) AF: 0.694 AC: 15505 AN: 22334

South Asian (SAS) AF: 0.459 AC: 12539 AN: 27328

European-Finnish (FIN) AF: 0.286 AC: 7755 AN: 27076

Middle Eastern (MID) AF: 0.444 AC: 754 AN: 1698

European-Non Finnish (NFE) AF: 0.318 AC: 73442 AN: 230608

Other (OTH) AF: 0.389 AC: 8339 AN: 21456

GnomAD4 genome AF: 0.401 AC: 60801 AN: 151524 Hom.: 12980 Cov.: 31 AF XY: 0.402 AC XY: 29767 AN XY: 74030

African (AFR) AF: 0.520 AC: 21477 AN: 41272

American (AMR) AF: 0.362 AC: 5521 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3468

East Asian (EAS) AF: 0.769 AC: 3899 AN: 5072

South Asian (SAS) AF: 0.451 AC: 2162 AN: 4790

European-Finnish (FIN) AF: 0.287 AC: 3021 AN: 10532

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21976 AN: 67852

Other (OTH) AF: 0.421 AC: 887 AN: 2106

Alfa AF: 0.354 Hom.: 13815

Bravo AF: 0.412

Asia WGS AF: 0.609 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.37
PhyloP100		-0.95
PromoterAI		-0.035	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

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