chr16-69133574-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.115A>Gā€‹(p.Thr39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

UTP4
NM_032830.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57
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=0.14336613).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTP4NM_032830.3 linkuse as main transcriptc.115A>G p.Thr39Ala missense_variant 2/17 ENST00000314423.12
UTP4XM_047434817.1 linkuse as main transcriptc.115A>G p.Thr39Ala missense_variant 2/10
UTP4NM_001318391.2 linkuse as main transcriptc.-135A>G 5_prime_UTR_variant 2/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTP4ENST00000314423.12 linkuse as main transcriptc.115A>G p.Thr39Ala missense_variant 2/171 NM_032830.3 P1Q969X6-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251416
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

UTP4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 19, 2023The UTP4 c.115A>G variant is predicted to result in the amino acid substitution p.Thr39Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-69167477-A-G). 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
0.075
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.10
.;T;.;.;.;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.028
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.73
T;T;T;T;T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.14
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.71
D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.94
.;N;N;N;N;N
REVEL
Benign
0.079
Sift
Benign
0.29
.;T;T;T;T;T
Sift4G
Benign
0.55
T;T;T;T;T;T
Polyphen
0.0, 0.0080
.;B;.;.;B;.
Vest4
0.17, 0.20, 0.18
MutPred
0.38
.;Loss of methylation at R35 (P = 0.1267);.;Loss of methylation at R35 (P = 0.1267);Loss of methylation at R35 (P = 0.1267);Loss of methylation at R35 (P = 0.1267);
MVP
0.55
MPC
0.18
ClinPred
0.13
T
GERP RS
3.7
Varity_R
0.079
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1030203914; hg19: chr16-69167477; COSMIC: COSV58734562; COSMIC: COSV58734562; API