chr20-63943668-C-T

Variant names:

• chr20-63943668-C-T
• NM_017859.4:c.908G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017859.4(UCKL1):​c.908G>A​(p.Arg303His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UCKL1 NM_017859.4 missense, splice_region
• Scores: Splicing: ADA: 0.4645
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3652168).

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.908G>A	p.Arg303His	missense splice_region	Exon 8 of 15	NP_060329.2	Q9NWZ5-1
	UCKL1	NM_001353477.2		c.905G>A	p.Arg302His	missense splice_region	Exon 8 of 15	NP_001340406.1
	UCKL1	NM_001193379.2		c.863G>A	p.Arg288His	missense splice_region	Exon 8 of 15	NP_001180308.1	Q9NWZ5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCKL1	ENST00000354216.11	TSL:1 MANE Select	c.908G>A	p.Arg303His	missense splice_region	Exon 8 of 15	ENSP00000346155.6	Q9NWZ5-1
	UCKL1	ENST00000969436.1		c.932G>A	p.Arg311His	missense splice_region	Exon 8 of 15	ENSP00000639495.1
	UCKL1	ENST00000969435.1		c.929G>A	p.Arg310His	missense splice_region	Exon 8 of 15	ENSP00000639494.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460324 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726454

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.11
Sift	Benign	0.37	T
Sift4G	Benign	0.38	T
Polyphen		0.049	B
Vest4		0.53
MutPred		0.34		Loss of phosphorylation at S306 (P = 0.0665)
MVP		0.59
MPC		1.6
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.71
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.46
dbscSNV1_RF	Benign	0.37
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

hg19: chr20-62575021;