chr16-69139852-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032830.3(UTP4):​c.464C>A​(p.Pro155His) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,613,794 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P155P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

UTP4
NM_032830.3 missense

Scores

3
8
7

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.61
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.023185968).
BP6
Variant 16-69139852-C-A is Benign according to our data. Variant chr16-69139852-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2890657.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTP4NM_032830.3 linkuse as main transcriptc.464C>A p.Pro155His missense_variant 5/17 ENST00000314423.12
UTP4NM_001318391.2 linkuse as main transcriptc.215C>A p.Pro72His missense_variant 5/17
UTP4XM_047434817.1 linkuse as main transcriptc.464C>A p.Pro155His missense_variant 5/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTP4ENST00000314423.12 linkuse as main transcriptc.464C>A p.Pro155His missense_variant 5/171 NM_032830.3 P1Q969X6-1

Frequencies

GnomAD3 genomes
AF:
0.000270
AC:
41
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00284
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000298
AC:
75
AN:
251474
Hom.:
0
AF XY:
0.000265
AC XY:
36
AN XY:
135912
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:
0.00319
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000116
AC:
170
AN:
1461644
Hom.:
1
Cov.:
29
AF XY:
0.000113
AC XY:
82
AN XY:
727134
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:
0.00256
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000269
AC:
41
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00284
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000790
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.000214
AC:
26
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

UTP4-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 26, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Pathogenic
0.15
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
.;T;.;.;T;.;.;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D;D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.023
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.58
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.9
.;D;D;.;.;D;N;.
REVEL
Benign
0.28
Sift
Uncertain
0.0080
.;D;D;.;.;D;D;.
Sift4G
Uncertain
0.0020
D;D;D;D;D;D;D;D
Polyphen
0.97, 1.0
.;D;.;.;.;.;D;.
Vest4
0.69, 0.72, 0.69
MVP
0.85
MPC
0.79
ClinPred
0.29
T
GERP RS
5.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.32
gMVP
0.50

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.

Other links and lift over

dbSNP: rs201153482; hg19: chr16-69173755; API