NM_080916.3:c.159G>A

Variant names:

• chr2-73938926-G-A
• rs62641680
• NM_080916.3:c.159G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_080916.3(DGUOK):​c.159G>A​(p.Thr53Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,022 control chromosomes in the GnomAD database, including 574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (30 hom., cov: 32)
  • Exomes 𝑓: 0.024 (544 hom.)
• Consequence: DGUOK NM_080916.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0730
• Publications: 10 publications found

Genes affected

DGUOK (HGNC:2858): (deoxyguanosine kinase) In mammalian cells, the phosphorylation of purine deoxyribonucleosides is mediated predominantly by two deoxyribonucleoside kinases, cytosolic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. The protein encoded by this gene is responsible for phosphorylation of purine deoxyribonucleosides in the mitochondrial matrix. In addition, this protein phosphorylates several purine deoxyribonucleoside analogs used in the treatment of lymphoproliferative disorders, and this phosphorylation is critical for the effectiveness of the analogs. Alternative splice variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DGUOK-AS1 (HGNC:43441): (DGUOK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 2-73938926-G-A is Benign according to our data. Variant chr2-73938926-G-A is described in ClinVar as Benign. ClinVar VariationId is 137080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.073 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0169 (2574/152262) while in subpopulation NFE AF = 0.0279 (1897/68020). AF 95% confidence interval is 0.0268. There are 30 homozygotes in GnomAd4. There are 1201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080916.3. 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
	DGUOK	NM_080916.3	MANE Select	c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 7	NP_550438.1	E5KSL5
	DGUOK	NM_080918.3		c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 5	NP_550440.1	Q16854-2
	DGUOK	NM_001318859.2		c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 5	NP_001305788.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGUOK	ENST00000264093.9	TSL:1 MANE Select	c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 7	ENSP00000264093.4	Q16854-1
	DGUOK	ENST00000418996.5	TSL:1	n.143-7793G>A		intron	N/A	ENSP00000408209.1	Q16854-6
	DGUOK	ENST00000893377.1		c.159G>A	p.Thr53Thr	synonymous	Exon 2 of 7	ENSP00000563436.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2576 AN: 152144 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00442

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0187 AC: 4702 AN: 251468 AF XY: 0.0190

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.00619

Gnomad ASJ exome AF: 0.00427

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0212

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.0245 AC: 35717 AN: 1460760 Hom.: 544 Cov.: 31 AF XY: 0.0239 AC XY: 17370 AN XY: 726766

African (AFR) AF: 0.00442 AC: 148 AN: 33458

American (AMR) AF: 0.00608 AC: 272 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 128 AN: 26124

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39676

South Asian (SAS) AF: 0.0120 AC: 1033 AN: 86246

European-Finnish (FIN) AF: 0.0228 AC: 1219 AN: 53402

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.0286 AC: 31729 AN: 1111010

Other (OTH) AF: 0.0194 AC: 1171 AN: 60356

GnomAD4 genome AF: 0.0169 AC: 2574 AN: 152262 Hom.: 30 Cov.: 32 AF XY: 0.0161 AC XY: 1201 AN XY: 74440

African (AFR) AF: 0.00440 AC: 183 AN: 41552

American (AMR) AF: 0.00785 AC: 120 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4830

European-Finnish (FIN) AF: 0.0225 AC: 238 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1897 AN: 68020

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0247 Hom.: 82

Bravo AF: 0.0154

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0239

EpiControl AF: 0.0226

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.073
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs62641680; hg19: chr2-74166053; COSMIC: COSV108037836;