20-63940064-AGG-A

Variant names:

• chr20-63940064-AGG-A
• rs35264801
• NM_017859.4:c.1568-11_1568-10delCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017859.4(UCKL1):​c.1568-11_1568-10delCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,482,034 control chromosomes in the GnomAD database, including 73 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (60 hom., cov: 0)
  • Exomes 𝑓: 0.15 (13 hom.)
• Consequence: UCKL1 NM_017859.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.715
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-63940064-AGG-A is Benign according to our data. Variant chr20-63940064-AGG-A is described in ClinVar as Benign. ClinVar VariationId is 770004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

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.1568-11_1568-10delCC		intron	N/A	NP_060329.2	Q9NWZ5-1
	UCKL1	NM_001353475.2		c.1571-11_1571-10delCC		intron	N/A	NP_001340404.1
	UCKL1	NM_001353476.2		c.1568-11_1568-10delCC		intron	N/A	NP_001340405.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCKL1	ENST00000354216.11	TSL:1 MANE Select	c.1568-11_1568-10delCC		intron	N/A	ENSP00000346155.6	Q9NWZ5-1
	UCKL1	ENST00000883271.1		c.1598-11_1598-10delCC		intron	N/A	ENSP00000553330.1
	UCKL1	ENST00000969434.1		c.1595-11_1595-10delCC		intron	N/A	ENSP00000639493.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 2426 AN: 121666 Hom.: 59 Cov.: 0

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00102

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.00562

Gnomad FIN AF: 0.00748

Gnomad MID AF: 0.00794

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.218 AC: 43636 AN: 199886 AF XY: 0.216

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.150 AC: 204284 AN: 1360302 Hom.: 13 AF XY: 0.150 AC XY: 101713 AN XY: 678216

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.283 AC: 8919 AN: 31492

American (AMR) AF: 0.243 AC: 10194 AN: 41928

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3779 AN: 24500

East Asian (EAS) AF: 0.313 AC: 11674 AN: 37280

South Asian (SAS) AF: 0.137 AC: 11258 AN: 82002

European-Finnish (FIN) AF: 0.128 AC: 5732 AN: 44744

Middle Eastern (MID) AF: 0.137 AC: 710 AN: 5198

European-Non Finnish (NFE) AF: 0.138 AC: 143066 AN: 1036738

Other (OTH) AF: 0.159 AC: 8952 AN: 56420

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0200 AC: 2439 AN: 121732 Hom.: 60 Cov.: 0 AF XY: 0.0197 AC XY: 1146 AN XY: 58270

African (AFR) AF: 0.0616 AC: 2002 AN: 32524

American (AMR) AF: 0.0137 AC: 167 AN: 12178

Ashkenazi Jewish (ASJ) AF: 0.00102 AC: 3 AN: 2942

East Asian (EAS) AF: 0.00985 AC: 40 AN: 4060

South Asian (SAS) AF: 0.00537 AC: 18 AN: 3354

European-Finnish (FIN) AF: 0.00748 AC: 53 AN: 7090

Middle Eastern (MID) AF: 0.00855 AC: 2 AN: 234

European-Non Finnish (NFE) AF: 0.00223 AC: 127 AN: 56970

Other (OTH) AF: 0.0162 AC: 27 AN: 1666

Alfa AF: 0.0981 Hom.: 411

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism

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: rs35264801; hg19: chr20-62571417; COSMIC: COSV105911981; COSMIC: COSV105911981;