15-72752882-G-T

Variant names:

• chr15-72752882-G-T
• rs368719480
• NM_001365225.1:c.953C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365225.1(ADPGK):​c.953C>A​(p.Ala318Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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. A318V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADPGK NM_001365225.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

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]

ACMG classification

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=0.15853107).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPGK	NM_001365225.1	MANE Select	c.953C>A	p.Ala318Glu	missense	Exon 7 of 7	NP_001352154.1	Q9BRR6-1
	ADPGK	NM_031284.5		c.950C>A	p.Ala317Glu	missense	Exon 7 of 7	NP_112574.3
	ADPGK	NM_001365226.1		c.587C>A	p.Ala196Glu	missense	Exon 7 of 7	NP_001352155.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPGK	ENST00000456471.3	TSL:1 MANE Select	c.953C>A	p.Ala318Glu	missense	Exon 7 of 7	ENSP00000397694.3	Q9BRR6-1
	ADPGK	ENST00000562621.1	TSL:1	n.3066C>A		non_coding_transcript_exon	Exon 2 of 2
	ADPGK	ENST00000567941.5	TSL:1	n.*926C>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000458102.1	Q9BRR6-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.93
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.11
Sift	Benign	0.27	T
Sift4G	Benign	0.27	T
Polyphen		0.14	B
Vest4		0.17
MVP		0.39
MPC		0.28
ClinPred		0.38	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368719480; hg19: chr15-73045223;