NM_017859.4:c.1040G>T

Variant names:

• chr20-63941026-C-A
• rs866887431
• NM_017859.4:c.1040G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017859.4(UCKL1):​c.1040G>T​(p.Arg347Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R347H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UCKL1 NM_017859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCKL1	NM_017859.4	c.1040G>T	p.Arg347Leu	missense_variant	Exon 10 of 15	ENST00000354216.11	NP_060329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCKL1	ENST00000354216.11	c.1040G>T	p.Arg347Leu	missense_variant	Exon 10 of 15	1	NM_017859.4	ENSP00000346155.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1414144 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 699788

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Uncertain	-0.015	T
MutationAssessor	Pathogenic	3.8	H;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.2	D;D;D
REVEL	Pathogenic	0.67
Sift	Benign	0.039	D;D;D
Sift4G	Uncertain	0.051	T;T;D
Polyphen		0.81	P;.;.
Vest4		0.82
MutPred		0.47		Loss of disorder (P = 0.0495);.;.;
MVP		0.57
MPC		1.9
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs866887431; hg19: chr20-62572379;