rs2252258

Positions:

• chr20-63945638-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UCKL1	NM_017859.4	c.654+13C>T		intron_variant		ENST00000354216.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCKL1	ENST00000354216.11	c.654+13C>T		intron_variant		1	NM_017859.4
UCKL1	ENST00000358711.7	c.654+13C>T		intron_variant		2
UCKL1	ENST00000369908.9	c.609+13C>T		intron_variant		2		P1
UCKL1	ENST00000632800.1	n.541+13C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.283 AC: 70678 AN: 249756 Hom.: 10741 AF XY: 0.279 AC XY: 37834 AN XY: 135490

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 SAS exome AF: 0.282

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

Gnomad4 AFR exome AF: 0.502

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.291

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

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.302

Alfa AF: 0.298 Hom.: 4724

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2252258; hg19: chr20-62576991; COSMIC: COSV62402502; COSMIC: COSV62402502;