4-70689353-C-T

Variant summary

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

The NM_020368.3(UTP3):​c.676C>T​(p.Leu226Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,614,010 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

UTP3
NM_020368.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585
Variant links:
Genes affected
UTP3 (HGNC:24477): (UTP3 small subunit processome component) Enables RNA binding activity. Predicted to be involved in brain development and maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10566747).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UTP3NM_020368.3 linkc.676C>T p.Leu226Phe missense_variant Exon 1 of 1 ENST00000254803.4 NP_065101.1 Q9NQZ2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UTP3ENST00000254803.4 linkc.676C>T p.Leu226Phe missense_variant Exon 1 of 1 6 NM_020368.3 ENSP00000254803.2 Q9NQZ2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
250934
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135686
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:
0.0000706
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.0000289
AC XY:
21
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:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000102
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
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
Oct 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.676C>T (p.L226F) alteration is located in exon 1 (coding exon 1) of the UTP3 gene. This alteration results from a C to T substitution at nucleotide position 676, causing the leucine (L) at amino acid position 226 to be replaced by a phenylalanine (F). 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
0.26
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0062
T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.050
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.10
Sift
Benign
0.45
T
Sift4G
Benign
0.24
T
Polyphen
0.012
B
Vest4
0.17
MutPred
0.46
Loss of stability (P = 0.1363);
MVP
0.51
MPC
0.45
ClinPred
0.070
T
GERP RS
5.4
Varity_R
0.052
gMVP
0.65

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.

Other links and lift over

dbSNP: rs753528938; hg19: chr4-71555070; API