Genetic Variant PDK1:p.Pro15Gln (chr2-172556194-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002610.5(PDK1):c.44C>A(p.Pro15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDK1
NM_002610.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.746

Publications

0 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:

ITGA6-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)

ITGA6-AS1 links:

PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)

PDK1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09511182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002610.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDK1	NM_002610.5	MANE Select	c.44C>A	p.Pro15Gln	missense	Exon 1 of 11	NP_002601.1	Q15118-1
PDK1	NM_001278549.2		c.44C>A	p.Pro15Gln	missense	Exon 1 of 12	NP_001265478.1	Q15118-2
PDK1	NR_103729.2		n.105C>A		non_coding_transcript_exon	Exon 1 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDK1	ENST00000282077.8	TSL:1 MANE Select	c.44C>A	p.Pro15Gln	missense	Exon 1 of 11	ENSP00000282077.3	Q15118-1
PDK1	ENST00000392571.6	TSL:1	c.44C>A	p.Pro15Gln	missense	Exon 1 of 12	ENSP00000376352.2	Q15118-2
PDK1	ENST00000410055.5	TSL:1	c.44C>A	p.Pro15Gln	missense	Exon 1 of 12	ENSP00000386985.1	Q15118-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1267786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

621274

African (AFR)

AF:

0.00

AC:

AN:

24928

American (AMR)

AF:

0.00

AC:

AN:

16100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19878

East Asian (EAS)

AF:

0.00

AC:

AN:

27630

South Asian (SAS)

AF:

0.00

AC:

AN:

63306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026136

Other (OTH)

AF:

0.00

AC:

AN:

52298

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.20

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.75

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.53

REVEL

Benign

0.069

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

0.0

Vest4

0.31

MutPred

0.18

Gain of MoRF binding (P = 0.0338)

MVP

0.35

MPC

0.31

ClinPred

0.42

GERP RS

3.4

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.11

gMVP

0.43

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over