8-116771820-A-G

Variant names:

• chr8-116771820-A-G
• rs757594423
• NM_032334.3:c.728A>G

Variant summary

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

The NM_032334.3(UTP23):​c.728A>G​(p.Lys243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,428,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UTP23 NM_032334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

UTP23 (HGNC:28224): (UTP23 small subunit processome component) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Predicted to be involved in rRNA processing. Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

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=0.05815044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032334.3. 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
	UTP23	NM_032334.3	MANE Select	c.728A>G	p.Lys243Arg	missense	Exon 3 of 3	NP_115710.2	Q9BRU9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP23	ENST00000309822.7	TSL:1 MANE Select	c.728A>G	p.Lys243Arg	missense	Exon 3 of 3	ENSP00000308332.2	Q9BRU9-1
	UTP23	ENST00000940242.1		c.656A>G	p.Lys219Arg	missense	Exon 3 of 3	ENSP00000610301.1
	UTP23	ENST00000517814.1	TSL:2	c.363+1454A>G		intron	N/A	ENSP00000429962.1	E5RGP0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000138 AC: 3 AN: 217492 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.0000288

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1428862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710048

African (AFR) AF: 0.00 AC: 0 AN: 31024

American (AMR) AF: 0.00 AC: 0 AN: 35368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24382

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 79252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1103550

Other (OTH) AF: 0.0000170 AC: 1 AN: 58896

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000660 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PhyloP100		1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.031
Sift	Benign	0.23	T
Sift4G	Benign	0.52	T
Polyphen		0.047	B
Vest4		0.046
MutPred		0.13		Loss of ubiquitination at K243 (P = 0.0023)
MVP		0.17
MPC		0.21
ClinPred		0.052	T
GERP RS		4.6
Varity_R		0.076
gMVP		0.093
Mutation Taster		=96/4	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: rs757594423; hg19: chr8-117784059;