Genetic Variant ADPGK:p.Ala59Val (chr15-72783516-G-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_001365225.1(ADPGK):c.176C>T(p.Ala59Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADPGK
NM_001365225.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Publications

0 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:

ADPGK-AS1 (HGNC:44144): (ADPGK antisense RNA 1)

ADPGK-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=0.23008314).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365225.1. 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.176C>T	p.Ala59Val	missense	Exon 1 of 7	NP_001352154.1	Q9BRR6-1
ADPGK	NM_031284.5		c.176C>T	p.Ala59Val	missense	Exon 1 of 7	NP_112574.3
ADPGK	NM_001365227.1		c.176C>T	p.Ala59Val	missense	Exon 1 of 4	NP_001352156.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADPGK	ENST00000456471.3	TSL:1 MANE Select	c.176C>T	p.Ala59Val	missense	Exon 1 of 7	ENSP00000397694.3	Q9BRR6-1
ADPGK	ENST00000567941.5	TSL:1	n.176C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000458102.1	Q9BRR6-6
ADPGK	ENST00000957653.1		c.176C>T	p.Ala59Val	missense	Exon 1 of 7	ENSP00000627712.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1322152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

650262

African (AFR)

AF:

0.00

AC:

AN:

26570

American (AMR)

AF:

0.00

AC:

AN:

26754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22778

East Asian (EAS)

AF:

0.00

AC:

AN:

29864

South Asian (SAS)

AF:

0.00

AC:

AN:

72750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3918

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051862

Other (OTH)

AF:

0.00

AC:

AN:

54876

GnomAD4 genome

Cov.:

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

0.14

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Benign

0.94

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.045

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

2.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.92

REVEL

Benign

0.17

Sift

Benign

0.53

Sift4G

Benign

0.72

Polyphen

0.78

Vest4

0.41

MutPred

0.28

Gain of catalytic residue at A59 (P = 0.0343)

MVP

0.63

MPC

0.30

ClinPred

0.70

GERP RS

4.3

PromoterAI

-0.082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

gMVP

0.59

Mutation Taster

=66/34

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