Genetic Variant UTP4:p.Arg143Gly (chr16-69137876-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032830.3(UTP4):c.427C>G(p.Arg143Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,606,320 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UTP4
NM_032830.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP4	NM_032830.3 link	c.427C>G	p.Arg143Gly	missense_variant	Exon 4 of 17	ENST00000314423.12	NP_116219.2	Q969X6-1
UTP4	NM_001318391.2 link	c.178C>G	p.Arg60Gly	missense_variant	Exon 4 of 17		NP_001305320.1
UTP4	XM_047434817.1 link	c.427C>G	p.Arg143Gly	missense_variant	Exon 4 of 10		XP_047290773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP4	ENST00000314423.12 link	c.427C>G	p.Arg143Gly	missense_variant	Exon 4 of 17	1	NM_032830.3	ENSP00000327179.7		Q969X6-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251314

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

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

Eigen

Benign

-0.041

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.46

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

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

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

REVEL

Uncertain

0.32

Sift

Uncertain

0.0090

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

Sift4G

Uncertain

0.0080

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

Polyphen

0.99, 1.0

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

Vest4

0.53, 0.53, 0.55

MutPred

0.52

.;Loss of MoRF binding (P = 0.0115);.;.;.;Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);Loss of MoRF binding (P = 0.0115);.;

MVP

0.65

MPC

0.67

ClinPred

0.97

GERP RS

3.7

Varity_R

0.54

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over