rs12573590

Variant names:

• chr10-74161058-C-A
• rs12573590
• NM_006721.4:c.65+9715C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-74161058-C-A
• chr10-74161058-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006721.4(ADK):​c.65+9715C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 152,244 control chromosomes in the GnomAD database, including 41 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 0.018 (41 hom., cov: 32)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0178 (2712/152244) while in subpopulation NFE AF = 0.0256 (1744/68010). AF 95% confidence interval is 0.0246. There are 41 homozygotes in GnomAd4. There are 1325 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	NM_006721.4	MANE Select	c.65+9715C>A		intron	N/A	NP_006712.2
	ADK	NM_001202450.2		c.65+9715C>A		intron	N/A	NP_001189379.1
	ADK	NM_001369123.1		c.65+9715C>A		intron	N/A	NP_001356052.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.65+9715C>A		intron	N/A	ENSP00000443965.2
	ADK	ENST00000286621.7	TSL:1	c.65+9715C>A		intron	N/A	ENSP00000286621.3
	ADK	ENST00000672429.1		c.65+9715C>A		intron	N/A	ENSP00000500292.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2712 AN: 152126 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0183

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

GnomAD4 genome AF: 0.0178 AC: 2712 AN: 152244 Hom.: 41 Cov.: 32 AF XY: 0.0178 AC XY: 1325 AN XY: 74432

African (AFR) AF: 0.00474 AC: 197 AN: 41530

American (AMR) AF: 0.00810 AC: 124 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5190

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4832

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0256 AC: 1744 AN: 68010

Other (OTH) AF: 0.0176 AC: 37 AN: 2104

Alfa AF: 0.0145 Hom.: 3

Bravo AF: 0.0148

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.64
PhyloP100		-0.45
Mutation Taster		=100/0	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: rs12573590; hg19: chr10-75920816;