Genetic Variant NM_032175.4:c.607G>A (chr5-73570645-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032175.4(UTP15):c.607G>A(p.Val203Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000145 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

UTP15
NM_032175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035470247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4 link	c.607G>A	p.Val203Ile	missense_variant	Exon 6 of 13	ENST00000296792.9	NP_115551.2	Q8TED0-1
UTP15	NM_001284430.1 link	c.550G>A	p.Val184Ile	missense_variant	Exon 6 of 13		NP_001271359.1	Q8TED0-3
UTP15	NM_001284431.1 link	c.37G>A	p.Val13Ile	missense_variant	Exon 5 of 12		NP_001271360.1	Q8TED0-2
UTP15	XM_011543680.3 link	c.607G>A	p.Val203Ile	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.607G>A	p.Val203Ile	missense_variant	Exon 6 of 13	1	NM_032175.4	ENSP00000296792.4	Q8TED0-1
UTP15	ENST00000509005.5 link	c.685G>A	p.Val229Ile	missense_variant	Exon 5 of 12	2		ENSP00000421669.1	H0Y8P4
UTP15	ENST00000508491.1 link	c.550G>A	p.Val184Ile	missense_variant	Exon 6 of 13	2		ENSP00000424609.1	Q8TED0-3
UTP15	ENST00000543251.5 link	c.37G>A	p.Val13Ile	missense_variant	Exon 5 of 12	2		ENSP00000440796.1	Q8TED0-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251472

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000607

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:

0.000123

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000147

AC:

215

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000125

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.607G>A (p.V203I) alteration is located in exon 6 (coding exon 5) of the UTP15 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the valine (V) at amino acid position 203 to be replaced by an isoleucine (I). 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

0.075

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.28

N;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.040

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.060

B;.;.

Vest4

0.11

MVP

0.18

MPC

0.27

ClinPred

0.053

GERP RS

5.0

Varity_R

0.034

gMVP

0.061

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