Genetic Variant UTP23:p.Met54Arg (chr8-116766764-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. 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. 13/22 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

1 publications found

Variant links:

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]

UTP23 links:

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]

EIF3H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17458063).

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.161T>G	p.Met54Arg	missense	Exon 1 of 3	NP_115710.2	Q9BRU9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UTP23	ENST00000309822.7	TSL:1 MANE Select	c.161T>G	p.Met54Arg	missense	Exon 1 of 3	ENSP00000308332.2	Q9BRU9-1
EIF3H	ENST00000520813.1	TSL:4	c.-109A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000427908.1	E5RFW7
UTP23	ENST00000940242.1		c.161T>G	p.Met54Arg	missense	Exon 1 of 3	ENSP00000610301.1

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151784

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000420

AC:

AN:

190378

AF XY:

0.0000385

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000623

Gnomad OTH exome

AF:

0.000201

GnomAD4 exome

AF:

0.0000391

AC:

AN:

1430438

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

709220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32642

American (AMR)

AF:

0.0000513

AC:

AN:

39004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25460

East Asian (EAS)

AF:

0.00

AC:

AN:

37856

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50800

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000401

AC:

AN:

1096390

Other (OTH)

AF:

0.0000507

AC:

AN:

59210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67902

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0062

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

M_CAP

Benign

0.0099

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

2.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.60

REVEL

Benign

0.16

Sift

Benign

0.15

Sift4G

Benign

0.44

Polyphen

0.86

Vest4

0.68

MVP

0.48

MPC

0.38

ClinPred

0.16

GERP RS

4.3

PromoterAI

-0.0026

Neutral

(source)

Varity_R

0.71

gMVP

0.64

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over