8-116771675-A-C

Position:

• chr8-116771675-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000309822.7(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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.066 (412 hom., cov: 33)
  • Exomes 𝑓: 0.046 (2017 hom.)
• Consequence: UTP23 ENST00000309822.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.55

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP23	NM_032334.3	c.583A>C	p.Lys195Gln	missense_variant	3/3	ENST00000309822.7	NP_115710.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP23	ENST00000309822.7	c.583A>C	p.Lys195Gln	missense_variant	3/3	1	NM_032334.3	ENSP00000308332	P1

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

GnomAD3 exomes AF: 0.0538 AC: 13293 AN: 247232 Hom.: 505 AF XY: 0.0560 AC XY: 7495 AN XY: 133756

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 SAS exome AF: 0.0885

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

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0296

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0877

Gnomad4 FIN exome AF: 0.0670

Gnomad4 NFE exome AF: 0.0405

Gnomad4 OTH exome AF: 0.0545

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.0429

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0479 Hom.: 436

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 v4.3

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
MutationTaster	Benign	0.000075	P;P;P;P
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

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

Other links and lift over

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