20-63956329-G-A

Variant names:

• chr20-63956329-G-A
• rs201642402
• NM_017859.4:c.44C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353480.2(UCKL1):​c.-321C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,553,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: UCKL1 NM_001353480.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• 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]

UCKL1-AS1 (HGNC:31967): (UCKL1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096523106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353480.2. 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.44C>T	p.Thr15Met	missense	Exon 1 of 15	NP_060329.2	Q9NWZ5-1
	UCKL1	NM_001353480.2		c.-321C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001340409.1
	UCKL1	NM_001353481.2		c.-517C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001340410.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCKL1	ENST00000354216.11	TSL:1 MANE Select	c.44C>T	p.Thr15Met	missense	Exon 1 of 15	ENSP00000346155.6	Q9NWZ5-1
	UCKL1	ENST00000883271.1		c.44C>T	p.Thr15Met	missense	Exon 1 of 15	ENSP00000553330.1
	UCKL1	ENST00000969434.1		c.44C>T	p.Thr15Met	missense	Exon 1 of 15	ENSP00000639493.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000105 AC: 2 AN: 190052 AF XY: 0.00000943

Gnomad AFR exome AF: 0.000103

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000571 AC: 8 AN: 1401564 Hom.: 0 Cov.: 30 AF XY: 0.00000287 AC XY: 2 AN XY: 696182

African (AFR) AF: 0.0000694 AC: 2 AN: 28826

American (AMR) AF: 0.00 AC: 0 AN: 36838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24432

East Asian (EAS) AF: 0.00 AC: 0 AN: 32758

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1085532

Other (OTH) AF: 0.0000174 AC: 1 AN: 57470

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000211 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000250 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.53
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.026
Sift	Benign	0.043	D
Sift4G	Benign	0.11	T
Polyphen		0.034	B
Vest4		0.25
MutPred		0.20		Loss of glycosylation at T15 (P = 5e-04)
MVP		0.29
MPC		0.083
ClinPred		0.059	T
GERP RS		0.60
PromoterAI		0.097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.021
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201642402; hg19: chr20-62587682;