NM_017859.4:c.569G>A

Variant names:

• chr20-63945818-C-T
• rs140413290
• NM_017859.4:c.569G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017859.4(UCKL1):​c.569G>A​(p.Arg190Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,613,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: UCKL1 NM_017859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.41
• Publications: 2 publications found

Genes affected

UCKL1 (HGNC:15938): (uridine-cytidine kinase 1 like 1) The protein encoded by this gene is a uridine kinase. Uridine kinases catalyze the phosphorylation of uridine to uridine monophosphate. This protein has been shown to bind to Epstein-Barr nuclear antigen 3 as well as natural killer lytic-associated molecule. Ubiquitination of this protein is enhanced by the presence of natural killer lytic-associated molecule. In addition, protein levels decrease in the presence of natural killer lytic-associated molecule, suggesting that association with natural killer lytic-associated molecule results in ubiquitination and subsequent degradation of this protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017859.4. 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
	UCKL1	NM_017859.4	MANE Select	c.569G>A	p.Arg190Gln	missense	Exon 4 of 15	NP_060329.2	Q9NWZ5-1
	UCKL1	NM_001353475.2		c.569G>A	p.Arg190Gln	missense	Exon 4 of 15	NP_001340404.1
	UCKL1	NM_001353476.2		c.566G>A	p.Arg189Gln	missense	Exon 4 of 15	NP_001340405.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCKL1	ENST00000354216.11	TSL:1 MANE Select	c.569G>A	p.Arg190Gln	missense	Exon 4 of 15	ENSP00000346155.6	Q9NWZ5-1
	UCKL1	ENST00000883271.1		c.593G>A	p.Arg198Gln	missense	Exon 4 of 15	ENSP00000553330.1
	UCKL1	ENST00000969434.1		c.593G>A	p.Arg198Gln	missense	Exon 4 of 15	ENSP00000639493.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 11 AN: 250812 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000938 AC: 137 AN: 1461288 Hom.: 0 Cov.: 33 AF XY: 0.0000949 AC XY: 69 AN XY: 726910

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86256

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52898

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000935 AC: 104 AN: 1111944

Other (OTH) AF: 0.000116 AC: 7 AN: 60384

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74462

African (AFR) AF: 0.0000481 AC: 2 AN: 41550

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	4.6	H
PhyloP100		7.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.93
MVP		0.86
MPC		2.1
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.93
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs140413290; hg19: chr20-62577171;