rs947598402

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002610.5(PDK1):c.50C>A(p.Pro17Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 1,414,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

PDK1
NM_002610.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.122

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:

Genome browser will be placed here

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=0.115971655).

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.50C>A	p.Pro17Gln	missense	Exon 1 of 11	NP_002601.1	Q15118-1
PDK1	NM_001278549.2		c.50C>A	p.Pro17Gln	missense	Exon 1 of 12	NP_001265478.1	Q15118-2
PDK1	NR_103729.2		n.111C>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.50C>A	p.Pro17Gln	missense	Exon 1 of 11	ENSP00000282077.3	Q15118-1
PDK1	ENST00000392571.6	TSL:1	c.50C>A	p.Pro17Gln	missense	Exon 1 of 12	ENSP00000376352.2	Q15118-2
PDK1	ENST00000410055.5	TSL:1	c.50C>A	p.Pro17Gln	missense	Exon 1 of 12	ENSP00000386985.1	Q15118-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

32032

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000634

AC:

AN:

1262510

Hom.:

Cov.:

AF XY:

0.00000485

AC XY:

AN XY:

618286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24644

American (AMR)

AF:

0.00

AC:

AN:

14438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19560

East Asian (EAS)

AF:

0.00

AC:

AN:

27612

South Asian (SAS)

AF:

0.00

AC:

AN:

62462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3810

European-Non Finnish (NFE)

AF:

0.00000781

AC:

AN:

1024264

Other (OTH)

AF:

0.00

AC:

AN:

52056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.8

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.22

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.12

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.46

REVEL

Benign

0.029

Sift

Benign

0.089

Sift4G

Uncertain

0.031

Polyphen

0.17

Vest4

0.21

MutPred

0.17

Gain of MoRF binding (P = 0.0287)

MVP

0.36

MPC

0.31

ClinPred

0.061

GERP RS

1.0

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.030

gMVP

0.34

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over