10-74176475-G-T

Variant names:

• chr10-74176475-G-T
• rs571962706
• NM_006721.4:c.66-24289G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006721.4(ADK):​c.66-24289G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 987,478 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.66-24289G>T		intron	N/A	NP_006712.2
	ADK	NM_001202450.2		c.66-24289G>T		intron	N/A	NP_001189379.1	P55263-3
	ADK	NM_001369123.1		c.66-24289G>T		intron	N/A	NP_001356052.1	A0A5F9ZH31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.66-24289G>T		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.66-24289G>T		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000960305.1		c.66-24289G>T		intron	N/A	ENSP00000630364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000203 AC: 2 AN: 987478 Hom.: 0 Cov.: 27 AF XY: 0.00000214 AC XY: 1 AN XY: 466690

African (AFR) AF: 0.00 AC: 0 AN: 18640

American (AMR) AF: 0.00 AC: 0 AN: 7824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9258

East Asian (EAS) AF: 0.00 AC: 0 AN: 12368

South Asian (SAS) AF: 0.00 AC: 0 AN: 39032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2276

European-Non Finnish (NFE) AF: 0.00000234 AC: 2 AN: 853026

Other (OTH) AF: 0.00 AC: 0 AN: 36094

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.059
DANN	Benign	0.80
PhyloP100		-2.9
PromoterAI		-0.17	Neutral

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: rs571962706; hg19: chr10-75936233;