rs16888728

Variant names:

• chr8-116771736-C-T
• rs16888728
• NM_032334.3:c.644C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032334.3(UTP23):​c.644C>T​(p.Pro215Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,611,740 control chromosomes in the GnomAD database, including 13,253 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3427 hom., cov: 33)
  • Exomes 𝑓: 0.10 (9826 hom.)
• Consequence: UTP23 NM_032334.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.74
• Publications: 25 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003584206).
• BP6: Variant 8-116771736-C-T is Benign according to our data. Variant chr8-116771736-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 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.644C>T	p.Pro215Leu	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.644C>T	p.Pro215Leu	missense	Exon 3 of 3	ENSP00000308332.2
	UTP23	ENST00000940242.1		c.572C>T	p.Pro191Leu	missense	Exon 3 of 3	ENSP00000610301.1
	UTP23	ENST00000517814.1	TSL:2	c.363+1370C>T		intron	N/A	ENSP00000429962.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26415 AN: 151782 Hom.: 3425 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.116 AC: 28810 AN: 247972 AF XY: 0.116

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.0590

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.0163

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0975

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.105 AC: 153269 AN: 1459840 Hom.: 9826 Cov.: 32 AF XY: 0.106 AC XY: 77249 AN XY: 726168

African (AFR) AF: 0.372 AC: 12324 AN: 33152

American (AMR) AF: 0.0634 AC: 2813 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4135 AN: 26082

East Asian (EAS) AF: 0.0262 AC: 1041 AN: 39658

South Asian (SAS) AF: 0.163 AC: 13957 AN: 85684

European-Finnish (FIN) AF: 0.114 AC: 6066 AN: 53300

Middle Eastern (MID) AF: 0.165 AC: 950 AN: 5744

European-Non Finnish (NFE) AF: 0.0940 AC: 104530 AN: 1111546

Other (OTH) AF: 0.124 AC: 7453 AN: 60300

GnomAD4 genome AF: 0.174 AC: 26454 AN: 151900 Hom.: 3427 Cov.: 33 AF XY: 0.172 AC XY: 12770 AN XY: 74268

African (AFR) AF: 0.368 AC: 15209 AN: 41360

American (AMR) AF: 0.102 AC: 1563 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3472

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5182

South Asian (SAS) AF: 0.154 AC: 739 AN: 4808

European-Finnish (FIN) AF: 0.114 AC: 1202 AN: 10532

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.0975 AC: 6626 AN: 67964

Other (OTH) AF: 0.149 AC: 316 AN: 2114

Alfa AF: 0.113 Hom.: 4192

Bravo AF: 0.179

TwinsUK AF: 0.105 AC: 391

ALSPAC AF: 0.0900 AC: 347

ESP6500AA AF: 0.357 AC: 1571

ESP6500EA AF: 0.0981 AC: 843

ExAC AF: 0.125 AC: 15179

Asia WGS AF: 0.130 AC: 455 AN: 3476

EpiCase AF: 0.0966

EpiControl AF: 0.0937

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.72
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.047
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.0040	B
Vest4		0.050
MPC		0.24
ClinPred		0.0025	T
GERP RS		-0.54
Varity_R		0.049
gMVP		0.10
Mutation Taster		=92/8	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: rs16888728; hg19: chr8-117783975; COSMIC: COSV59124379; COSMIC: COSV59124379;