rs73147065

chr20-63942653-A-Cchr20-63942653-A-Gchr20-63942653-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017859.4(UCKL1):c.923+1000T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 510,766 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0064 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (29 hom.)
• Consequence: UCKL1 NM_017859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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]

MIR647 (HGNC:32903): (microRNA 647) 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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCKL1	NM_017859.4	c.923+1000T>G		intron_variant		ENST00000354216.11
MIR647	NR_030377.1	n.74T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCKL1	ENST00000354216.11	c.923+1000T>G		intron_variant		1	NM_017859.4
MIR647	ENST00000384823.1	n.74T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 976 AN: 151754 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.00427

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00676 AC: 1357 AN: 200626 Hom.: 11 AF XY: 0.00721 AC XY: 784 AN XY: 108732

Gnomad AFR exome AF: 0.00170

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00839

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00689

Gnomad FIN exome AF: 0.00606

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.00765

GnomAD4 exome AF: 0.00771 AC: 2766 AN: 358894 Hom.: 29 Cov.: 4 AF XY: 0.00784 AC XY: 1560 AN XY: 198962

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.00814

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00711

Gnomad4 FIN exome AF: 0.00538

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.00689

GnomAD4 genome AF: 0.00643 AC: 976 AN: 151872 Hom.: 6 Cov.: 32 AF XY: 0.00605 AC XY: 449 AN XY: 74206

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00872

Gnomad4 FIN AF: 0.00427

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00483 Hom.: 348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.6
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs73147065; hg19: chr20-62574006;