dbSNP rs530143335: UCKL1:p.Ile289Thr (chr20-63944437-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UCKL1	NM_017859.4	MANE Select	c.866T>C	p.Ile289Thr	missense	Exon 7 of 15	NP_060329.2	Q9NWZ5-1
UCKL1	NM_001353475.2		c.866T>C	p.Ile289Thr	missense	Exon 7 of 15	NP_001340404.1
UCKL1	NM_001353476.2		c.863T>C	p.Ile288Thr	missense	Exon 7 of 15	NP_001340405.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UCKL1	ENST00000354216.11	TSL:1 MANE Select	c.866T>C	p.Ile289Thr	missense	Exon 7 of 15	ENSP00000346155.6	Q9NWZ5-1
UCKL1	ENST00000883271.1		c.890T>C	p.Ile297Thr	missense	Exon 7 of 15	ENSP00000553330.1
UCKL1	ENST00000969434.1		c.890T>C	p.Ile297Thr	missense	Exon 7 of 15	ENSP00000639493.1

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

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

196170

AF XY:

0.00000945

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 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

African (AFR)

AF:

0.00

AC:

AN:

29296

American (AMR)

AF:

0.0000270

AC:

AN:

37010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21252

East Asian (EAS)

AF:

0.00

AC:

AN:

29716

South Asian (SAS)

AF:

0.00

AC:

AN:

80192

European-Finnish (FIN)

AF:

0.0000244

AC:

AN:

41020

Middle Eastern (MID)

AF:

0.000430

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.0000404

AC:

AN:

990552

Other (OTH)

AF:

0.0000197

AC:

AN:

50864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000415

AC:

AN:

144424

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

70294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40230

American (AMR)

AF:

0.00

AC:

AN:

14658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3350

East Asian (EAS)

AF:

0.00

AC:

AN:

4288

South Asian (SAS)

AF:

0.00

AC:

AN:

4064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000917

AC:

AN:

65428

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000841

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.8

PhyloP100

7.0

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.53

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0010

Polyphen

0.74

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

Mutation Taster

=30/70

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over