10-74176853-C-T

Variant names:

• chr10-74176853-C-T
• rs10824095
• ENST00000372734.5:c.-20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001123.4(ADK):​c.-20C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,607,474 control chromosomes in the GnomAD database, including 421,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41960 hom., cov: 33)
  • Exomes 𝑓: 0.72 (379830 hom.)
• Consequence: ADK NM_001123.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.751
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-74176853-C-T is Benign according to our data. Variant chr10-74176853-C-T is described in ClinVar as Benign. ClinVar VariationId is 300835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123.4. 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.66-23911C>T		intron	N/A	NP_006712.2
	ADK	NM_001123.4		c.-20C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001114.2
	ADK	NM_001202449.2		c.-20C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001189378.1	P55263-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000372734.5	TSL:1	c.-20C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000361819.3	P55263-2
	ADK	ENST00000372734.5	TSL:1	c.-20C>T		5_prime_UTR	Exon 1 of 11	ENSP00000361819.3	P55263-2
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.66-23911C>T		intron	N/A	ENSP00000443965.2	P55263-1

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111934 AN: 152040 Hom.: 41926 Cov.: 33

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.782

GnomAD2 exomes AF: 0.674 AC: 160279 AN: 237720 AF XY: 0.676

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.872

Gnomad EAS exome AF: 0.370

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.724

GnomAD4 exome AF: 0.717 AC: 1044036 AN: 1455316 Hom.: 379830 Cov.: 77 AF XY: 0.714 AC XY: 517427 AN XY: 724340

African (AFR) AF: 0.790 AC: 26453 AN: 33474

American (AMR) AF: 0.602 AC: 26863 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 22723 AN: 26102

East Asian (EAS) AF: 0.392 AC: 15555 AN: 39672

South Asian (SAS) AF: 0.557 AC: 48012 AN: 86176

European-Finnish (FIN) AF: 0.674 AC: 32012 AN: 47502

Middle Eastern (MID) AF: 0.846 AC: 4871 AN: 5760

European-Non Finnish (NFE) AF: 0.741 AC: 823750 AN: 1111694

Other (OTH) AF: 0.726 AC: 43797 AN: 60288

GnomAD4 genome AF: 0.736 AC: 112022 AN: 152158 Hom.: 41960 Cov.: 33 AF XY: 0.727 AC XY: 54102 AN XY: 74374

African (AFR) AF: 0.790 AC: 32806 AN: 41548

American (AMR) AF: 0.708 AC: 10823 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3015 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2046 AN: 5156

South Asian (SAS) AF: 0.537 AC: 2597 AN: 4834

European-Finnish (FIN) AF: 0.662 AC: 7013 AN: 10590

Middle Eastern (MID) AF: 0.849 AC: 248 AN: 292

European-Non Finnish (NFE) AF: 0.754 AC: 51215 AN: 67966

Other (OTH) AF: 0.775 AC: 1639 AN: 2114

Alfa AF: 0.765 Hom.: 7880

Bravo AF: 0.738

Asia WGS AF: 0.486 AC: 1696 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Adenosine kinase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.9
DANN	Benign	0.92
PhyloP100		-0.75
PromoterAI		0.049	Neutral
Mutation Taster		=300/0	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: rs10824095; hg19: chr10-75936611; COSMIC: COSV54206867;