rs10509348

Variant names:

• chr10-74382759-G-A
• rs10509348
• NM_006721.4:c.274-11382G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006721.4(ADK):​c.274-11382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,808 control chromosomes in the GnomAD database, including 32,450 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (32450 hom., cov: 30)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 3 publications found

Genes affected

ADK (HGNC:257): (adenosine kinase) This gene an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ADK Gene-Disease associations (from GenCC):

• adenosine kinase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006721.4. 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
	ADK	NM_006721.4	MANE Select	c.274-11382G>A		intron	N/A	NP_006712.2
	ADK	NM_001123.4		c.223-11382G>A		intron	N/A	NP_001114.2
	ADK	NM_001202449.2		c.169-11382G>A		intron	N/A	NP_001189378.1	P55263-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.274-11382G>A		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.274-11382G>A		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000372734.5	TSL:1	c.223-11382G>A		intron	N/A	ENSP00000361819.3	P55263-2

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96999 AN: 151692 Hom.: 32456 Cov.: 30

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.706

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.639 AC: 97032 AN: 151808 Hom.: 32450 Cov.: 30 AF XY: 0.634 AC XY: 47018 AN XY: 74168

African (AFR) AF: 0.467 AC: 19328 AN: 41386

American (AMR) AF: 0.664 AC: 10126 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2918 AN: 3468

East Asian (EAS) AF: 0.414 AC: 2133 AN: 5148

South Asian (SAS) AF: 0.526 AC: 2520 AN: 4794

European-Finnish (FIN) AF: 0.647 AC: 6803 AN: 10512

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50875 AN: 67938

Other (OTH) AF: 0.701 AC: 1474 AN: 2104

Alfa AF: 0.679 Hom.: 6242

Bravo AF: 0.630

Asia WGS AF: 0.461 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs10509348; hg19: chr10-76142517;