16-69143186-G-A

Variant names:

• chr16-69143186-G-A
• NM_032830.3:c.535G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032830.3(UTP4):​c.535G>A​(p.Val179Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP4 NM_032830.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039266348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP4	NM_032830.3	c.535G>A	p.Val179Ile	missense_variant	Exon 6 of 17	ENST00000314423.12	NP_116219.2
UTP4	NM_001318391.2	c.286G>A	p.Val96Ile	missense_variant	Exon 6 of 17		NP_001305320.1
UTP4	XM_005256205.4	c.118G>A	p.Val40Ile	missense_variant	Exon 2 of 13		XP_005256262.2
UTP4	XM_047434817.1	c.535G>A	p.Val179Ile	missense_variant	Exon 6 of 10		XP_047290773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP4	ENST00000314423.12	c.535G>A	p.Val179Ile	missense_variant	Exon 6 of 17	1	NM_032830.3	ENSP00000327179.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.17
DANN	Benign	0.79
DEOGEN2	Benign	0.043	T;.;.;T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.60	T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.039	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.27	N;N;.;.;N;N
REVEL	Benign	0.020
Sift	Benign	0.37	T;T;.;.;T;T
Sift4G	Benign	0.45	T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;.;B
Vest4		0.066
MutPred		0.27		Loss of ubiquitination at K174 (P = 0.0957);.;.;.;Loss of ubiquitination at K174 (P = 0.0957);Loss of ubiquitination at K174 (P = 0.0957);
MVP		0.22
MPC		0.15
ClinPred		0.047	T
GERP RS		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.012
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-69177089;