Genetic Variant UCK2:p.Ser70Leu (chr1-165890313-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012474.5(UCK2):c.209C>T(p.Ser70Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

UCK2
NM_012474.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

UCK2 (HGNC:12562): (uridine-cytidine kinase 2) This gene encodes a pyrimidine ribonucleoside kinase. The encoded protein (EC 2.7.1.48) catalyzes phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP), respectively.[provided by RefSeq, Oct 2010]

UCK2 links:

ENSG00000236364 (HGNC:):

ENSG00000236364 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12601414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCK2	NM_012474.5 link	c.209C>T	p.Ser70Leu	missense_variant	Exon 2 of 7	ENST00000367879.9	NP_036606.2	Q9BZX2-1
UCK2	NM_001363568.2 link	c.146C>T	p.Ser49Leu	missense_variant	Exon 3 of 8		NP_001350497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UCK2	ENST00000367879.9 link	c.209C>T	p.Ser70Leu	missense_variant	Exon 2 of 7	1	NM_012474.5	ENSP00000356853.4	Q9BZX2-1
UCK2	ENST00000642653.1 link	c.146C>T	p.Ser49Leu	missense_variant	Exon 3 of 8			ENSP00000494961.1	A0A2R8Y653
ENSG00000236364	ENST00000626270.2 link	n.2208G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152004

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251468

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74224

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.209C>T (p.S70L) alteration is located in exon 2 (coding exon 2) of the UCK2 gene. This alteration results from a C to T substitution at nucleotide position 209, causing the serine (S) at amino acid position 70 to be replaced by a leucine (L). 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

Benign

0.073

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.079

Sift

Uncertain

0.024

D;.

Sift4G

Benign

0.14

T;.

Polyphen

0.0070

B;.

Vest4

0.17

MutPred

0.45

Loss of disorder (P = 0.0274);.;

MVP

0.043

MPC

0.95

ClinPred

0.26

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.20

gMVP

0.58

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