chr16-69136806-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_032830.3(UTP4):​c.270G>A​(p.Ala90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,140 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00089 ( 8 hom. )

Consequence

UTP4
NM_032830.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.184
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 Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 16-69136806-G-A is Benign according to our data. Variant chr16-69136806-G-A is described in ClinVar as [Benign]. Clinvar id is 887042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.184 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UTP4NM_032830.3 linkuse as main transcriptc.270G>A p.Ala90= synonymous_variant 3/17 ENST00000314423.12
UTP4NM_001318391.2 linkuse as main transcriptc.21G>A p.Ala7= synonymous_variant 3/17
UTP4XM_047434817.1 linkuse as main transcriptc.270G>A p.Ala90= synonymous_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UTP4ENST00000314423.12 linkuse as main transcriptc.270G>A p.Ala90= synonymous_variant 3/171 NM_032830.3 P1Q969X6-1

Frequencies

GnomAD3 genomes
AF:
0.00459
AC:
698
AN:
152176
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0153
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
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:
0.000500
Gnomad OTH
AF:
0.00575
GnomAD3 exomes
AF:
0.00143
AC:
359
AN:
251496
Hom.:
7
AF XY:
0.000964
AC XY:
131
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.0169
Gnomad AMR exome
AF:
0.00116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000360
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000889
AC:
1300
AN:
1461846
Hom.:
8
Cov.:
32
AF XY:
0.000804
AC XY:
585
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0144
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000627
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
AF:
0.00460
AC:
700
AN:
152294
Hom.:
4
Cov.:
32
AF XY:
0.00415
AC XY:
309
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0153
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000500
Gnomad4 OTH
AF:
0.00569
Alfa
AF:
0.00265
Hom.:
3
Bravo
AF:
0.00498
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000415

ClinVar

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

Submissions by phenotype

Hereditary North American Indian childhood cirrhosis Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 16, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
2.0
DANN
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs16958656; hg19: chr16-69170709; API