15-72783537-G-T

Variant names:

• chr15-72783537-G-T
• rs763964371
• NM_001365225.1:c.155C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365225.1(ADPGK):​c.155C>A​(p.Ser52Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000224 in 1,338,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S52F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: ADPGK NM_001365225.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33637127).

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.155C>A	p.Ser52Tyr	missense	Exon 1 of 7	NP_001352154.1	Q9BRR6-1
	ADPGK	NM_031284.5		c.155C>A	p.Ser52Tyr	missense	Exon 1 of 7	NP_112574.3
	ADPGK	NM_001365227.1		c.155C>A	p.Ser52Tyr	missense	Exon 1 of 4	NP_001352156.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPGK	ENST00000456471.3	TSL:1 MANE Select	c.155C>A	p.Ser52Tyr	missense	Exon 1 of 7	ENSP00000397694.3	Q9BRR6-1
	ADPGK	ENST00000567941.5	TSL:1	n.155C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000458102.1	Q9BRR6-6
	ADPGK	ENST00000957653.1		c.155C>A	p.Ser52Tyr	missense	Exon 1 of 7	ENSP00000627712.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000224 AC: 30 AN: 1338256 Hom.: 0 Cov.: 31 AF XY: 0.0000182 AC XY: 12 AN XY: 659026

African (AFR) AF: 0.00 AC: 0 AN: 27084

American (AMR) AF: 0.00 AC: 0 AN: 30216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23658

East Asian (EAS) AF: 0.00 AC: 0 AN: 30336

South Asian (SAS) AF: 0.00 AC: 0 AN: 74822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4018

European-Non Finnish (NFE) AF: 0.0000255 AC: 27 AN: 1059244

Other (OTH) AF: 0.0000538 AC: 3 AN: 55726

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	28
DANN	Benign	0.94
Eigen	Benign	0.089
Eigen_PC	Benign	0.0069
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.048	D
Polyphen		0.99	D
Vest4		0.23
MutPred		0.32		Loss of glycosylation at S52 (P = 3e-04)
MVP		0.68
MPC		0.41
ClinPred		0.84	D
GERP RS		2.0
PromoterAI		-0.0084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.79
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs763964371; hg19: chr15-73075878;