20-63939983-G-T

Variant names:

• chr20-63939983-G-T
• NM_017859.4:c.1640C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017859.4(UCKL1):​c.1640C>A​(p.Thr547Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UCKL1 NM_017859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06824064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCKL1	NM_017859.4	c.1640C>A	p.Thr547Lys	missense_variant	Exon 15 of 15	ENST00000354216.11	NP_060329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCKL1	ENST00000354216.11	c.1640C>A	p.Thr547Lys	missense_variant	Exon 15 of 15	1	NM_017859.4	ENSP00000346155.6
UCKL1	ENST00000369908.9	c.1595C>A	p.Thr532Lys	missense_variant	Exon 15 of 15	2		ENSP00000358924.5
UCKL1	ENST00000358711	c.*429C>A		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000351546.3
UCKL1	ENST00000632800.1	n.*114C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459734 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726144

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.021
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.089	B;.
Vest4		0.17
MutPred		0.20		Gain of ubiquitination at T547 (P = 0.0031);.;
MVP		0.20
MPC		1.0
ClinPred		0.086	T
GERP RS		-4.4
Varity_R		0.048
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
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: chr20-62571336;