rs1133950

Variant names:

• chr8-116771675-A-C
• rs1133950
• NM_032334.3:c.583A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032334.3(UTP23):​c.583A>C​(p.Lys195Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,610,856 control chromosomes in the GnomAD database, including 2,429 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 0.066 (412 hom., cov: 33)
  • Exomes 𝑓: 0.046 (2017 hom.)
• Consequence: UTP23 NM_032334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.55
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001796186).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

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.583A>C	p.Lys195Gln	missense	Exon 3 of 3	NP_115710.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP23	ENST00000309822.7	TSL:1 MANE Select	c.583A>C	p.Lys195Gln	missense	Exon 3 of 3	ENSP00000308332.2
	UTP23	ENST00000940242.1		c.511A>C	p.Lys171Gln	missense	Exon 3 of 3	ENSP00000610301.1
	UTP23	ENST00000517814.1	TSL:2	c.363+1309A>C		intron	N/A	ENSP00000429962.1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9976 AN: 152142 Hom.: 413 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.0660

GnomAD2 exomes AF: 0.0538 AC: 13293 AN: 247232 AF XY: 0.0560

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.0281

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.000608

Gnomad FIN exome AF: 0.0661

Gnomad NFE exome AF: 0.0450

Gnomad OTH exome AF: 0.0618

GnomAD4 exome AF: 0.0465 AC: 67765 AN: 1458596 Hom.: 2017 Cov.: 31 AF XY: 0.0479 AC XY: 34759 AN XY: 725500

African (AFR) AF: 0.115 AC: 3816 AN: 33058

American (AMR) AF: 0.0296 AC: 1303 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2631 AN: 26032

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39660

South Asian (SAS) AF: 0.0877 AC: 7477 AN: 85238

European-Finnish (FIN) AF: 0.0670 AC: 3574 AN: 53366

Middle Eastern (MID) AF: 0.107 AC: 615 AN: 5744

European-Non Finnish (NFE) AF: 0.0405 AC: 45055 AN: 1111286

Other (OTH) AF: 0.0545 AC: 3280 AN: 60206

GnomAD4 genome AF: 0.0655 AC: 9974 AN: 152260 Hom.: 412 Cov.: 33 AF XY: 0.0665 AC XY: 4952 AN XY: 74444

African (AFR) AF: 0.113 AC: 4693 AN: 41538

American (AMR) AF: 0.0491 AC: 751 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0805 AC: 389 AN: 4830

European-Finnish (FIN) AF: 0.0667 AC: 706 AN: 10592

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0429 AC: 2920 AN: 68026

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0512 Hom.: 892

Bravo AF: 0.0638

TwinsUK AF: 0.0515 AC: 191

ALSPAC AF: 0.0355 AC: 137

ESP6500AA AF: 0.107 AC: 470

ESP6500EA AF: 0.0405 AC: 348

ExAC AF: 0.0572 AC: 6944

Asia WGS AF: 0.0380 AC: 136 AN: 3478

EpiCase AF: 0.0445

EpiControl AF: 0.0439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		8.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.17
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.98	D
Vest4		0.12
MPC		0.52
ClinPred		0.034	T
GERP RS		5.6
Varity_R		0.50
gMVP		0.37
Mutation Taster		=88/12	polymorphism (auto)

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: rs1133950; hg19: chr8-117783914; COSMIC: COSV59124270; COSMIC: COSV59124270;