15-72755567-T-C

Variant names:

• chr15-72755567-T-C
• rs2066100851
• NM_001365225.1:c.928A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365225.1(ADPGK):​c.928A>G​(p.Ile310Val) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I310T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADPGK NM_001365225.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23129323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADPGK	NM_001365225.1	c.928A>G	p.Ile310Val	missense_variant	Exon 6 of 7	ENST00000456471.3	NP_001352154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADPGK	ENST00000456471.3	c.928A>G	p.Ile310Val	missense_variant	Exon 6 of 7	1	NM_001365225.1	ENSP00000397694.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.928A>G (p.I310V) alteration is located in exon 6 (coding exon 6) of the ADPGK gene. This alteration results from a A to G substitution at nucleotide position 928, causing the isoleucine (I) at amino acid position 310 to be replaced by a valine (V). 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	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.97
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.000074
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.084
Sift	Benign	0.49	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.34	B;B
Vest4		0.25
MutPred		0.74		Gain of disorder (P = 0.1109);.;
MVP		0.52
MPC		0.21
ClinPred		0.33	T
GERP RS		3.7
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs2066100851; hg19: chr15-73047908;