chr16-69136838-G-T

Position:

chr16-69136838-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032830.3(UTP4):c.302G>T(p.Gly101Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,614,160 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 13 hom. )

Consequence

UTP4
NM_032830.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 9.03

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]

UTP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02347508).

BP6

Variant 16-69136838-G-T is Benign according to our data. Variant chr16-69136838-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 710240.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UTP4	NM_032830.3 linkuse as main transcript	c.302G>T	p.Gly101Val	missense_variant	3/17	ENST00000314423.12
UTP4	NM_001318391.2 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	3/17
UTP4	XM_047434817.1 linkuse as main transcript	c.302G>T	p.Gly101Val	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP4	ENST00000314423.12 linkuse as main transcript	c.302G>T	p.Gly101Val	missense_variant	3/17	1	NM_032830.3	P1	Q969X6-1

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

346

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00223

AC:

561

AN:

251488

Hom.:

AF XY:

0.00232

AC XY:

316

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00362

AC:

5287

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

2594

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000927

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00428

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.00227

AC:

346

AN:

152312

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00267

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00200

AC:

243

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00308

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary North American Indian childhood cirrhosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

UTP4-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 21, 2021

This 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 submitter

clinical testing

Invitae

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.34

.;T;.;.;T;.;.;T;T

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.023

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.34

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.8

.;D;D;.;.;D;D;D;.

REVEL

Uncertain

0.63

Sift

Uncertain

0.014

.;D;D;.;.;D;D;D;.

Sift4G

Pathogenic

0.0

D;T;D;D;D;T;D;T;D

Polyphen

1.0

.;D;.;.;.;.;D;.;.

Vest4

0.85, 0.87, 0.86

MVP

0.86

MPC

0.83

ClinPred

0.065

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.88

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over