rs2252258

Variant names:

• chr20-63945638-G-A
• rs2252258
• NM_017859.4:c.654+13C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017859.4(UCKL1):​c.654+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,611,604 control chromosomes in the GnomAD database, including 70,416 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 0.33 (9059 hom., cov: 33)
  • Exomes 𝑓: 0.29 (61357 hom.)
• Consequence: UCKL1 NM_017859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCKL1	NM_017859.4	c.654+13C>T		intron_variant	Intron 5 of 14	ENST00000354216.11	NP_060329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCKL1	ENST00000354216.11	c.654+13C>T		intron_variant	Intron 5 of 14	1	NM_017859.4	ENSP00000346155.6

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50406 AN: 151982 Hom.: 9042 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.283 AC: 70678 AN: 249756 AF XY: 0.279

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.316

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.286 AC: 417925 AN: 1459504 Hom.: 61357 Cov.: 35 AF XY: 0.285 AC XY: 206962 AN XY: 725978

African (AFR) AF: 0.502 AC: 16791 AN: 33462

American (AMR) AF: 0.221 AC: 9887 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 7014 AN: 26100

East Asian (EAS) AF: 0.325 AC: 12890 AN: 39670

South Asian (SAS) AF: 0.278 AC: 24004 AN: 86214

European-Finnish (FIN) AF: 0.238 AC: 12446 AN: 52280

Middle Eastern (MID) AF: 0.278 AC: 1599 AN: 5762

European-Non Finnish (NFE) AF: 0.284 AC: 315743 AN: 1110992

Other (OTH) AF: 0.291 AC: 17551 AN: 60340

GnomAD4 genome AF: 0.332 AC: 50460 AN: 152100 Hom.: 9059 Cov.: 33 AF XY: 0.328 AC XY: 24354 AN XY: 74342

African (AFR) AF: 0.493 AC: 20424 AN: 41470

American (AMR) AF: 0.227 AC: 3472 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 942 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1640 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1341 AN: 4832

European-Finnish (FIN) AF: 0.252 AC: 2671 AN: 10596

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19052 AN: 67966

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.301 Hom.: 17403

Bravo AF: 0.336

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.034
DANN	Benign	0.75
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs2252258; hg19: chr20-62576991; COSMIC: COSV62402502; COSMIC: COSV62402502;