Genetic Variant UTP15:p.Ala55Val (chr5-73568308-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001284431.1(UTP15):c.-407C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000343 in 1,456,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

UTP15
NM_001284431.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3677706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4 link	c.164C>T	p.Ala55Val	missense_variant	Exon 3 of 13	ENST00000296792.9	NP_115551.2	Q8TED0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9 link	c.164C>T	p.Ala55Val	missense_variant	Exon 3 of 13	1	NM_032175.4	ENSP00000296792.4		Q8TED0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248914

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000221

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1456778

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164C>T (p.A55V) alteration is located in exon 3 (coding exon 2) of the UTP15 gene. This alteration results from a C to T substitution at nucleotide position 164, causing the alanine (A) at amino acid position 55 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

.;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.18

Sift

Benign

0.12

T;T;T

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

1.0

.;D;.

Vest4

0.51, 0.48

MutPred

0.61

Loss of disorder (P = 0.1258);Loss of disorder (P = 0.1258);.;

MVP

0.26

MPC

1.0

ClinPred

0.90

GERP RS

4.6

Varity_R

0.45

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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