chr8-116771601-A-G

Position:

• chr8-116771601-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032334.3(UTP23):​c.509A>G​(p.His170Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00242 in 1,612,568 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (42 hom.)
• Consequence: UTP23 NM_032334.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.07

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004047394).
• BP6: Variant 8-116771601-A-G is Benign according to our data. Variant chr8-116771601-A-G is described in ClinVar as [Benign]. Clinvar id is 776379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2052/152312) while in subpopulation AFR AF= 0.0475 (1972/41554). AF 95% confidence interval is 0.0457. There are 56 homozygotes in gnomad4. There are 973 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP23	NM_032334.3	c.509A>G	p.His170Arg	missense_variant	3/3	ENST00000309822.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP23	ENST00000309822.7	c.509A>G	p.His170Arg	missense_variant	3/3	1	NM_032334.3	P1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2042 AN: 152194 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00343 AC: 855 AN: 249348 Hom.: 16 AF XY: 0.00234 AC XY: 315 AN XY: 134680

Gnomad AFR exome AF: 0.0486

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00127 AC: 1855 AN: 1460256 Hom.: 42 Cov.: 31 AF XY: 0.00108 AC XY: 783 AN XY: 726276

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.00155

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.0135 AC: 2052 AN: 152312 Hom.: 56 Cov.: 33 AF XY: 0.0131 AC XY: 973 AN XY: 74492

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00223 Hom.: 11

Bravo AF: 0.0148

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0458 AC: 202

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00434 AC: 527

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Benign	0.35	T
Sift4G	Benign	0.35	T
Polyphen		0.75	P
Vest4		0.20
MVP		0.44
MPC		0.29
ClinPred		0.054	T
GERP RS		4.8
Varity_R		0.40
gMVP		0.16

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: rs16888722; hg19: chr8-117783840;