Genetic Variant ADPGK:p.Tyr155Cys (chr15-72771841-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001365229.1(ADPGK):c.-254A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000744 in 1,612,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ADPGK
NM_001365229.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

Publications

1 publications found

Variant links:

Genes affected

ADPGK (HGNC:25250): (ADP dependent glucokinase) ADPGK (EC 2.7.1.147) catalyzes the ADP-dependent phosphorylation of glucose to glucose-6-phosphate and may play a role in glycolysis, possibly during ischemic conditions (Ronimus and Morgan, 2004 [PubMed 14975750]).[supplied by OMIM, Mar 2008]

ADPGK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.851

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365229.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADPGK	NM_001365225.1	MANE Select	c.464A>G	p.Tyr155Cys	missense	Exon 3 of 7	NP_001352154.1	Q9BRR6-1
ADPGK	NM_001365229.1		c.-254A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001352158.1	Q9BRR6-3
ADPGK	NM_031284.5		c.464A>G	p.Tyr155Cys	missense	Exon 3 of 7	NP_112574.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADPGK	ENST00000456471.3	TSL:1 MANE Select	c.464A>G	p.Tyr155Cys	missense	Exon 3 of 7	ENSP00000397694.3	Q9BRR6-1
ADPGK	ENST00000567941.5	TSL:1	n.*440A>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000458102.1	Q9BRR6-6
ADPGK	ENST00000567941.5	TSL:1	n.*440A>G		3_prime_UTR	Exon 3 of 7	ENSP00000458102.1	Q9BRR6-6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00000803

AC:

AN:

248974

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460382

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.0000224

AC:

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111258

Other (OTH)

AF:

0.0000166

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000131

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000828

AC:

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

0.26

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.7

PhyloP100

4.8

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.45

Sift

Uncertain

0.016

Sift4G

Benign

0.070

Polyphen

1.0

Vest4

0.94

MutPred

0.79

Loss of disorder (P = 0.1325)

MVP

0.79

MPC

0.91

ClinPred

0.98

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.86

Mutation Taster

=58/42

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over