rs144369314

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G101A) has been classified as Uncertain significance.

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

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

hereditary North American Indian childhood cirrhosis
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
cirrhosis, familial
Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

UTP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 710240.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032830.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP4	NM_032830.3	MANE Select	c.302G>T	p.Gly101Val	missense	Exon 3 of 17	NP_116219.2	Q969X6-1
	UTP4	NM_001318391.2		c.53G>T	p.Gly18Val	missense	Exon 3 of 17	NP_001305320.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UTP4	ENST00000314423.12	TSL:1 MANE Select	c.302G>T	p.Gly101Val	missense	Exon 3 of 17	ENSP00000327179.7	Q969X6-1
UTP4	ENST00000562237.5	TSL:1	c.344G>T	p.Gly115Val	missense	Exon 3 of 17	ENSP00000456709.1	H3BSH7
UTP4	ENST00000960037.1		c.302G>T	p.Gly101Val	missense	Exon 3 of 17	ENSP00000630096.1

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

GnomAD2 exomes

AF:

0.00223

AC:

561

AN:

251488

AF XY:

0.00232

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 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

African (AFR)

AF:

0.000508

AC:

AN:

33478

American (AMR)

AF:

0.00335

AC:

150

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000927

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000524

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00428

AC:

4757

AN:

1111984

Other (OTH)

AF:

0.00353

AC:

213

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

295

589

884

1178

1473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00227

AC:

346

AN:

152312

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41564

American (AMR)

AF:

0.00373

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00348

AC:

237

AN:

68038

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00300

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary North American Indian childhood cirrhosis (1)

not provided (1)

UTP4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.072

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.34

PhyloP100

9.0

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.63

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.85

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

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over