7-95593507-A-G

Position:

• chr7-95593507-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.344+192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 152,184 control chromosomes in the GnomAD database, including 520 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 0.076 (520 hom., cov: 32)
• Consequence: PDK4 NM_002612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDK4	NM_002612.4	c.344+192T>C		intron_variant		ENST00000005178.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDK4	ENST00000005178.6	c.344+192T>C		intron_variant		1	NM_002612.4	P1
PDK4-AS1	ENST00000665332.1	n.37-19544A>G		intron_variant, non_coding_transcript_variant
PDK4-AS1	ENST00000667350.1	n.90-13433A>G		intron_variant, non_coding_transcript_variant
PDK4-AS1	ENST00000669019.1	n.63-17037A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11567 AN: 152066 Hom.: 520 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0760 AC: 11567 AN: 152184 Hom.: 520 Cov.: 32 AF XY: 0.0816 AC XY: 6074 AN XY: 74392

Gnomad4 AFR AF: 0.0577

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0730

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0732 Hom.: 598

Bravo AF: 0.0667

Asia WGS AF: 0.156 AC: 542 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3779478; hg19: chr7-95222819;