Genetic Variant UTP15:p.Cys253Gly (chr5-73572572-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032175.4(UTP15):c.757T>G(p.Cys253Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000231 in 1,614,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

UTP15
NM_032175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

UTP15 (HGNC:25758): (UTP15 small subunit processome component) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in endoplasmic reticulum and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

UTP15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2633494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4 link	c.757T>G	p.Cys253Gly	missense_variant	Exon 7 of 13	ENST00000296792.9	NP_115551.2	Q8TED0-1
UTP15	NM_001284430.1 link	c.700T>G	p.Cys234Gly	missense_variant	Exon 7 of 13		NP_001271359.1	Q8TED0-3
UTP15	NM_001284431.1 link	c.187T>G	p.Cys63Gly	missense_variant	Exon 6 of 12		NP_001271360.1	Q8TED0-2
UTP15	XM_011543680.3 link	c.757T>G	p.Cys253Gly	missense_variant	Exon 7 of 13		XP_011541982.1	Q8TED0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9 link	c.757T>G	p.Cys253Gly	missense_variant	Exon 7 of 13	1	NM_032175.4	ENSP00000296792.4		Q8TED0-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

251448

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00115

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

319

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

150

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00148

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000355

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.757T>G (p.C253G) alteration is located in exon 7 (coding exon 6) of the UTP15 gene. This alteration results from a T to G substitution at nucleotide position 757, causing the cysteine (C) at amino acid position 253 to be replaced by a glycine (G). 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

Benign

0.22

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.027

D;T;D

Sift4G

Uncertain

0.028

D;D;D

Polyphen

0.81

P;.;.

Vest4

0.66

MVP

0.63

MPC

0.87

ClinPred

0.35

GERP RS

5.8

Varity_R

0.57

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over