8-116766764-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032334.3(UTP23):c.161T>G(p.Met54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,582,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: UTP23 NM_032334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97

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]

EIF3H (HGNC:3273): (eukaryotic translation initiation factor 3 subunit H) Enables deubiquitinase activity. Contributes to translation initiation factor activity. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process and translational initiation. Located in extracellular exosome and membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in breast cancer; prostate cancer; and prostate carcinoma. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17458063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP23	NM_032334.3	c.161T>G	p.Met54Arg	missense_variant	1/3	ENST00000309822.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP23	ENST00000309822.7	c.161T>G	p.Met54Arg	missense_variant	1/3	1	NM_032334.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151784 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.0000420 AC: 8 AN: 190378 Hom.: 0 AF XY: 0.0000385 AC XY: 4 AN XY: 103934

Gnomad AFR exome AF: 0.0000939

Gnomad AMR exome AF: 0.0000367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000623

Gnomad OTH exome AF: 0.000201

GnomAD4 exome AF: 0.0000391 AC: 56 AN: 1430438 Hom.: 0 Cov.: 31 AF XY: 0.0000451 AC XY: 32 AN XY: 709220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000513

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000401

Gnomad4 OTH exome AF: 0.0000507

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151904 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74262

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000167 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.161T>G (p.M54R) alteration is located in exon 1 (coding exon 1) of the UTP23 gene. This alteration results from a T to G substitution at nucleotide position 161, causing the methionine (M) at amino acid position 54 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.17
Cadd	Benign	23
Dann	Benign	0.96
DEOGEN2	Benign	0.0062	T;T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T;T;D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.60	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.86	P;.;.
Vest4		0.68
MVP		0.48
MPC		0.38
ClinPred		0.16	T
GERP RS		4.3
Varity_R		0.71
gMVP		0.64

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: rs537971398; hg19: chr8-117779003;