Variant 15-72771811-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365225.1(ADPGK):c.494A>G(p.Gln165Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADPGK
NM_001365225.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADPGK	NM_001365225.1 linkuse as main transcript	c.494A>G	p.Gln165Arg	missense_variant	3/7	ENST00000456471.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADPGK	ENST00000456471.3 linkuse as main transcript	c.494A>G	p.Gln165Arg	missense_variant	3/7	1	NM_001365225.1	P4	Q9BRR6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461136

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.494A>G (p.Q165R) alteration is located in exon 3 (coding exon 3) of the ADPGK gene. This alteration results from a A to G substitution at nucleotide position 494, causing the glutamine (Q) at amino acid position 165 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.0099

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.29

Sift

Uncertain

0.029

D;D

Sift4G

Benign

0.37

T;.

Polyphen

0.98

D;.

Vest4

0.80

MutPred

0.65

Gain of methylation at Q165 (P = 0.0341);.;

MVP

0.75

MPC

0.27

ClinPred

0.93

GERP RS

5.8

gMVP

0.91

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over