1-165907794-G-T

Variant names:

• chr1-165907794-G-T
• rs1647720130
• NM_012474.5:c.757G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012474.5(UCK2):​c.757G>T​(p.Ala253Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A253T) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UCK2 NM_012474.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

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]

MIR3658 (HGNC:38963): (microRNA 3658) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022280723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012474.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCK2	NM_012474.5	MANE Select	c.757G>T	p.Ala253Ser	missense	Exon 7 of 7	NP_036606.2
	UCK2	NM_001363568.2		c.694G>T	p.Ala232Ser	missense	Exon 8 of 8	NP_001350497.1	A0A2R8Y653
	MIR3658	NR_037431.1		n.-127G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCK2	ENST00000367879.9	TSL:1 MANE Select	c.757G>T	p.Ala253Ser	missense	Exon 7 of 7	ENSP00000356853.4	Q9BZX2-1
	UCK2	ENST00000470820.1	TSL:1	c.307G>T	p.Ala103Ser	missense	Exon 4 of 4	ENSP00000476327.1	Q9BZX2-2
	UCK2	ENST00000462329.5	TSL:1	n.524G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.80
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.069
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.042
Sift	Benign	0.87	T
Sift4G	Benign	0.81	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.21		Gain of phosphorylation at A253 (P = 0.0037)
MVP		0.068
MPC		1.0
ClinPred		0.022	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.024
gMVP		0.40
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1647720130; hg19: chr1-165877031;