16-69139866-A-G

Variant summary

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

The NM_032830.3(UTP4):ā€‹c.478A>Gā€‹(p.Ile160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

UTP4
NM_032830.3 missense

Scores

1
17

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.331
Variant links:
Genes affected
UTP4 (HGNC:1983): (UTP4 small subunit processome component) This gene encodes a WD40-repeat-containing protein that is localized to the nucleolus. Mutation of this gene causes North American Indian childhood cirrhosis, a severe intrahepatic cholestasis that results in transient neonatal jaundice, and progresses to periportal fibrosis and cirrhosis in childhood and adolescence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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=0.13446268).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTP4NM_032830.3 linkuse as main transcriptc.478A>G p.Ile160Val missense_variant 5/17 ENST00000314423.12
UTP4NM_001318391.2 linkuse as main transcriptc.229A>G p.Ile77Val missense_variant 5/17
UTP4XM_047434817.1 linkuse as main transcriptc.478A>G p.Ile160Val missense_variant 5/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTP4ENST00000314423.12 linkuse as main transcriptc.478A>G p.Ile160Val missense_variant 5/171 NM_032830.3 P1Q969X6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461758
Hom.:
0
Cov.:
29
AF XY:
0.00000688
AC XY:
5
AN XY:
727192
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:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

UTP4-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 07, 2023The UTP4 c.478A>G variant is predicted to result in the amino acid substitution p.Ile160Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
10
DANN
Benign
0.96
DEOGEN2
Benign
0.074
.;T;.;.;T;.;.;T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.32
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.68
T;T;T;T;T;T;T;T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.97
D;D;D
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.94
.;N;N;.;.;N;N;.
REVEL
Benign
0.074
Sift
Benign
0.16
.;T;T;.;.;T;T;.
Sift4G
Benign
0.18
T;T;T;T;T;T;T;T
Polyphen
0.044, 0.0050
.;B;.;.;.;.;B;.
Vest4
0.17, 0.20
MutPred
0.46
.;Gain of glycosylation at S156 (P = 0.1127);.;.;.;Gain of glycosylation at S156 (P = 0.1127);Gain of glycosylation at S156 (P = 0.1127);.;
MVP
0.40
MPC
0.18
ClinPred
0.11
T
GERP RS
0.53
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.058
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs1962914300; hg19: chr16-69173769; API