rs119465999

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_032830.3(UTP4):c.1693C>T(p.Arg565Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,614,032 control chromosomes in the GnomAD database, including 11 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 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 9 hom. )

Consequence

UTP4
NM_032830.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 1.85

Publications

23 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012974888).

BP6

Variant 16-69165386-C-T is Benign according to our data. Variant chr16-69165386-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 3194.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000918 (1342/1461884) while in subpopulation AMR AF = 0.016 (717/44724). AF 95% confidence interval is 0.0151. There are 9 homozygotes in GnomAdExome4. There are 642 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 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.1693C>T	p.Arg565Trp	missense	Exon 15 of 17	NP_116219.2	Q969X6-1
	UTP4	NM_001318391.2		c.1444C>T	p.Arg482Trp	missense	Exon 15 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.1693C>T	p.Arg565Trp	missense	Exon 15 of 17	ENSP00000327179.7	Q969X6-1
UTP4	ENST00000562237.5	TSL:1	c.1735C>T	p.Arg579Trp	missense	Exon 15 of 17	ENSP00000456709.1	H3BSH7
UTP4	ENST00000960037.1		c.1804C>T	p.Arg602Trp	missense	Exon 15 of 17	ENSP00000630096.1

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

235

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00325

AC:

818

AN:

251478

AF XY:

0.00267

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000918

AC:

1342

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000883

AC XY:

642

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.0160

AC:

717

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

299

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.00168

AC:

145

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000872

AC:

AN:

1112006

Other (OTH)

AF:

0.00116

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00155

AC:

236

AN:

152148

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41488

American (AMR)

AF:

0.0108

AC:

165

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00104

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68010

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000877

Hom.:

Bravo

AF:

0.00206

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00245

AC:

298

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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 (2)

not provided (1)

UTP4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.42

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.89

PhyloP100

1.9

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.80

MVP

0.78

MPC

0.76

ClinPred

0.085

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.50

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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