20-63943668-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCKL1	NM_017859.4	c.908G>A	p.Arg303His	missense_variant, splice_region_variant	Exon 8 of 15	ENST00000354216.11	NP_060329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCKL1	ENST00000354216.11	c.908G>A	p.Arg303His	missense_variant, splice_region_variant	Exon 8 of 15	1	NM_017859.4	ENSP00000346155.6
UCKL1	ENST00000369908.9	c.863G>A	p.Arg288His	missense_variant, splice_region_variant	Exon 8 of 15	2		ENSP00000358924.5
UCKL1	ENST00000358711.7	c.906+729G>A		intron_variant	Intron 7 of 12	2		ENSP00000351546.3
UCKL1	ENST00000632800.1	n.795G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 7 of 14	5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.908G>A (p.R303H) alteration is located in exon 8 (coding exon 8) of the UCKL1 gene. This alteration results from a G to A substitution at nucleotide position 908, causing the arginine (R) at amino acid position 303 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.11
Sift	Benign	0.37	T;T
Sift4G	Benign	0.38	T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62575021;