20-63942653-A-G

Variant names:

• chr20-63942653-A-G
• rs73147065
• NM_017859.4:c.923+1000T>C

Variant summary

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

The NM_017859.4(UCKL1):​c.923+1000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 510,228 control chromosomes in the GnomAD database, including 11,310 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 0.24 (5562 hom., cov: 32)
  • Exomes 𝑓: 0.17 (5748 hom.)
• Consequence: UCKL1 NM_017859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 13 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]

MIR647 (HGNC:32903): (microRNA 647) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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.923+1000T>C		intron	N/A	NP_060329.2	Q9NWZ5-1
	UCKL1	NM_001353475.2		c.907-164T>C		intron	N/A	NP_001340404.1
	UCKL1	NM_001353476.2		c.904-164T>C		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.923+1000T>C		intron	N/A	ENSP00000346155.6	Q9NWZ5-1
	UCKL1	ENST00000883271.1		c.931-161T>C		intron	N/A	ENSP00000553330.1
	UCKL1	ENST00000969434.1		c.931-164T>C		intron	N/A	ENSP00000639493.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36991 AN: 151720 Hom.: 5541 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.175 AC: 35152 AN: 200626 AF XY: 0.168

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.167 AC: 59954 AN: 358390 Hom.: 5748 Cov.: 4 AF XY: 0.162 AC XY: 32138 AN XY: 198736

African (AFR) AF: 0.417 AC: 4011 AN: 9608

American (AMR) AF: 0.132 AC: 4252 AN: 32100

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 1640 AN: 10912

East Asian (EAS) AF: 0.142 AC: 1553 AN: 10918

South Asian (SAS) AF: 0.121 AC: 7582 AN: 62550

European-Finnish (FIN) AF: 0.256 AC: 7373 AN: 28766

Middle Eastern (MID) AF: 0.146 AC: 396 AN: 2718

European-Non Finnish (NFE) AF: 0.164 AC: 30530 AN: 185600

Other (OTH) AF: 0.172 AC: 2617 AN: 15218

GnomAD4 genome AF: 0.244 AC: 37052 AN: 151838 Hom.: 5562 Cov.: 32 AF XY: 0.242 AC XY: 17960 AN XY: 74186

African (AFR) AF: 0.427 AC: 17671 AN: 41364

American (AMR) AF: 0.159 AC: 2428 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.144 AC: 740 AN: 5154

South Asian (SAS) AF: 0.109 AC: 526 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10546

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11851 AN: 67942

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.137 Hom.: 348

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.78
PhyloP100		-0.12
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		4.0
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: rs73147065; hg19: chr20-62574006; COSMIC: COSV62402899; COSMIC: COSV62402899;