chr15-72774909-T-A

Position:

• chr15-72774909-T-A

Variant summary

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

The NM_001365225.1(ADPGK):​c.422A>T​(p.Asp141Val) 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. 14/19 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. D141N) 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: 2.35

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=0.13554427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADPGK	NM_001365225.1	c.422A>T	p.Asp141Val	missense_variant	2/7	ENST00000456471.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADPGK	ENST00000456471.3	c.422A>T	p.Asp141Val	missense_variant	2/7	1	NM_001365225.1	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2024

The c.422A>T (p.D141V) alteration is located in exon 2 (coding exon 2) of the ADPGK gene. This alteration results from a A to T substitution at nucleotide position 422, causing the aspartic acid (D) at amino acid position 141 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	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.077	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.15
Sift	Benign	0.27	T;T
Sift4G	Benign	0.22	T;.
Polyphen		0.050	B;.
Vest4		0.44
MutPred		0.43		Loss of disorder (P = 0.0644);.;
MVP		0.51
MPC		0.35
ClinPred		0.26	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.72

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.

Other links and lift over

hg19: chr15-73067250;