20-63956273-C-A

Variant names:

• chr20-63956273-C-A
• rs1269408167
• NM_017859.4:c.100G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017859.4(UCKL1):​c.100G>T​(p.Ala34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: UCKL1 NM_017859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036498845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCKL1	NM_017859.4	c.100G>T	p.Ala34Ser	missense_variant	Exon 1 of 15	ENST00000354216.11	NP_060329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCKL1	ENST00000354216.11	c.100G>T	p.Ala34Ser	missense_variant	Exon 1 of 15	1	NM_017859.4	ENSP00000346155.6
UCKL1	ENST00000358711.7	c.100G>T	p.Ala34Ser	missense_variant	Exon 1 of 13	2		ENSP00000351546.3
UCKL1	ENST00000483710.1	n.69G>T		non_coding_transcript_exon_variant	Exon 1 of 3	3
UCKL1-AS1	ENST00000623569.1	n.2890C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1398918 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 694056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000550

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: 9.21e-7

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.0
DANN	Benign	0.93
DEOGEN2	Benign	0.065	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.44	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.34	N;N
REVEL	Benign	0.058
Sift	Benign	0.81	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.0010	B;.
Vest4		0.12
MutPred		0.14		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.18
MPC		0.074
ClinPred		0.052	T
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1269408167; hg19: chr20-62587626;