Genetic Variant NM_032175.4:c.109G>A (chr5-73568253-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_032175.4(UTP15):c.109G>A(p.Glu37Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,609,998 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 0.00039 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

UTP15
NM_032175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.77

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39274484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4 link	c.109G>A	p.Glu37Lys	missense_variant	Exon 3 of 13	ENST00000296792.9	NP_115551.2	Q8TED0-1
UTP15	XM_011543680.3 link	c.109G>A	p.Glu37Lys	missense_variant	Exon 3 of 13		XP_011541982.1	Q8TED0-1
UTP15	NM_001284431.1 link	c.-462G>A		5_prime_UTR_variant	Exon 2 of 12		NP_001271360.1	Q8TED0-2
UTP15	NM_001284430.1 link	c.91-39G>A		intron_variant	Intron 2 of 12		NP_001271359.1	Q8TED0-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9 link	c.109G>A	p.Glu37Lys	missense_variant	Exon 3 of 13	1	NM_032175.4	ENSP00000296792.4		Q8TED0-1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000352

AC:

AN:

250180

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.000722

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000676

AC:

986

AN:

1457754

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

486

AN XY:

725048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000772

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000762

Gnomad4 OTH exome

AF:

0.000798

GnomAD4 genome

AF:

0.000394

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000389

Hom.:

Bravo

AF:

0.000351

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000329

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109G>A (p.E37K) alteration is located in exon 3 (coding exon 2) of the UTP15 gene. This alteration results from a G to A substitution at nucleotide position 109, causing the glutamic acid (E) at amino acid position 37 to be replaced by a lysine (K). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.39

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.3

.;M

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.71

MVP

0.46

MPC

1.1

ClinPred

0.48

GERP RS

5.5

Varity_R

0.66

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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