Genetic Variant PDK1:c.*1533G>T (chr2-172597502-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002610.5(PDK1):c.*1533G>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 0.195 in 152,156 control chromosomes in the GnomAD database, including 3,710 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 0.20 ( 3710 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

PDK1
NM_002610.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

Publications

18 publications found

Variant links:

Genes affected

PDK1 (HGNC:8809): (pyruvate dehydrogenase kinase 1) Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

PDK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK1	NM_002610.5 link	c.*1533G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000282077.8	NP_002601.1	Q15118-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK1	ENST00000282077.8 link	c.*1533G>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_002610.5	ENSP00000282077.3		Q15118-1
PDK1	ENST00000410055.5 link	c.*55-111G>T		intron_variant	Intron 11 of 11	1		ENSP00000386985.1		Q15118-1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29641

AN:

152030

Hom.:

3703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.195

AC:

29689

AN:

152148

Hom.:

3710

Cov.:

AF XY:

0.192

AC XY:

14266

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.347

AC:

14400

AN:

41478

American (AMR)

AF:

0.125

AC:

1914

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

436

AN:

3468

East Asian (EAS)

AF:

0.0197

AC:

102

AN:

5182

South Asian (SAS)

AF:

0.141

AC:

681

AN:

4828

European-Finnish (FIN)

AF:

0.120

AC:

1267

AN:

10584

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.150

AC:

10207

AN:

68008

Other (OTH)

AF:

0.183

AC:

387

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1182

2364

3545

4727

5909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.158

Hom.:

2807

Bravo

AF:

0.202

Asia WGS

AF:

0.129

AC:

449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.64

PhyloP100

-0.061

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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2-172597502-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over