NM_002612.4:c.344+192T>C

Variant names:

• chr7-95593507-A-G
• rs3779478
• NM_002612.4:c.344+192T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	NM_002612.4	MANE Select	c.344+192T>C		intron	N/A	NP_002603.1	A4D1H4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	ENST00000005178.6	TSL:1 MANE Select	c.344+192T>C		intron	N/A	ENSP00000005178.5	Q16654
	PDK4	ENST00000886049.1		c.344+192T>C		intron	N/A	ENSP00000556108.1
	PDK4	ENST00000886050.1		c.338+192T>C		intron	N/A	ENSP00000556109.1

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

African (AFR) AF: 0.0577 AC: 2398 AN: 41542

American (AMR) AF: 0.0432 AC: 660 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3470

East Asian (EAS) AF: 0.152 AC: 785 AN: 5180

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4820

European-Finnish (FIN) AF: 0.115 AC: 1220 AN: 10584

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0730 AC: 4965 AN: 67980

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0723 Hom.: 829

Bravo AF: 0.0667

Asia WGS AF: 0.156 AC: 542 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.84
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3779478; hg19: chr7-95222819;