Genetic Variant UTP15:p.Pro216Arg (chr5-73570685-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032175.4(UTP15):c.647C>G(p.Pro216Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

UTP15
NM_032175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4 link	c.647C>G	p.Pro216Arg	missense_variant	Exon 6 of 13	ENST00000296792.9	NP_115551.2	Q8TED0-1
UTP15	NM_001284430.1 link	c.590C>G	p.Pro197Arg	missense_variant	Exon 6 of 13		NP_001271359.1	Q8TED0-3
UTP15	NM_001284431.1 link	c.77C>G	p.Pro26Arg	missense_variant	Exon 5 of 12		NP_001271360.1	Q8TED0-2
UTP15	XM_011543680.3 link	c.647C>G	p.Pro216Arg	missense_variant	Exon 6 of 13		XP_011541982.1	Q8TED0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UTP15	ENST00000296792.9 link	c.647C>G	p.Pro216Arg	missense_variant	Exon 6 of 13	1	NM_032175.4	ENSP00000296792.4	Q8TED0-1
UTP15	ENST00000509005.5 link	c.725C>G	p.Pro242Arg	missense_variant	Exon 5 of 12	2		ENSP00000421669.1	H0Y8P4
UTP15	ENST00000508491.1 link	c.590C>G	p.Pro197Arg	missense_variant	Exon 6 of 13	2		ENSP00000424609.1	Q8TED0-3
UTP15	ENST00000543251.5 link	c.77C>G	p.Pro26Arg	missense_variant	Exon 5 of 12	2		ENSP00000440796.1	Q8TED0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251446

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135886

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:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727230

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:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.647C>G (p.P216R) alteration is located in exon 6 (coding exon 5) of the UTP15 gene. This alteration results from a C to G substitution at nucleotide position 647, causing the proline (P) at amino acid position 216 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

0.45

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

0.29

MutationAssessor

Pathogenic

3.0

M;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-8.9

D;D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.92

MutPred

0.59

Gain of MoRF binding (P = 0.0138);.;.;

MVP

0.68

MPC

1.1

ClinPred

1.0

GERP RS

6.2

Varity_R

0.93

gMVP

0.70

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