Variant 20-63944437-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017859.4(UCKL1):c.866T>C(p.Ile289Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000357 in 1,428,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

UCKL1
NM_017859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCKL1	NM_017859.4 linkuse as main transcript	c.866T>C	p.Ile289Thr	missense_variant	7/15	ENST00000354216.11	NP_060329.2	Q9NWZ5-1Q53HM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UCKL1	ENST00000354216.11 linkuse as main transcript	c.866T>C	p.Ile289Thr	missense_variant	7/15	1	NM_017859.4	ENSP00000346155.6	Q9NWZ5-1
UCKL1	ENST00000369908.9 linkuse as main transcript	c.821T>C	p.Ile274Thr	missense_variant	7/15	2		ENSP00000358924.5	Q9NWZ5-4
UCKL1	ENST00000358711.7 linkuse as main transcript	c.866T>C	p.Ile289Thr	missense_variant	7/13	2		ENSP00000351546.3	Q9NWZ5-2
UCKL1	ENST00000632800.1 linkuse as main transcript	n.753T>C		non_coding_transcript_exon_variant	6/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000416

AC:

AN:

144298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000917

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000153

AC:

AN:

196170

Hom.:

AF XY:

0.00000945

AC XY:

AN XY:

105828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000598

Gnomad NFE exome

AF:

0.0000238

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1284556

Hom.:

Cov.:

AF XY:

0.0000393

AC XY:

AN XY:

636334

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000270

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000244

Gnomad4 NFE exome

AF:

0.0000404

Gnomad4 OTH exome

AF:

0.0000197

GnomAD4 genome

AF:

0.0000415

AC:

AN:

144424

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

70294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000917

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000841

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2021

The c.866T>C (p.I289T) alteration is located in exon 7 (coding exon 7) of the UCKL1 gene. This alteration results from a T to C substitution at nucleotide position 866, causing the isoleucine (I) at amino acid position 289 to be replaced by a threonine (T). 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

0.63

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.8

M;M;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.74

P;.;.

Vest4

0.91

MVP

0.71

MPC

1.3

ClinPred

0.85

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over