16-69143266-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032830.3(UTP4):c.615C>T(p.Ser205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,614,126 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (32 hom.)
• Consequence: UTP4 NM_032830.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.83

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-69143266-C-T is Benign according to our data. Variant chr16-69143266-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 887045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP4	NM_032830.3	c.615C>T	p.Ser205=	synonymous_variant	6/17	ENST00000314423.12
UTP4	NM_001318391.2	c.366C>T	p.Ser122=	synonymous_variant	6/17
UTP4	XM_005256205.4	c.198C>T	p.Ser66=	synonymous_variant	2/13
UTP4	XM_047434817.1	c.615C>T	p.Ser205=	synonymous_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP4	ENST00000314423.12	c.615C>T	p.Ser205=	synonymous_variant	6/17	1	NM_032830.3	P1

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 538 AN: 152150 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00406 AC: 1022 AN: 251490 Hom.: 6 AF XY: 0.00373 AC XY: 507 AN XY: 135922

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0244

Gnomad NFE exome AF: 0.00388

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00377 AC: 5507 AN: 1461858 Hom.: 32 Cov.: 33 AF XY: 0.00355 AC XY: 2584 AN XY: 727240

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000536

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.00355

Gnomad4 OTH exome AF: 0.00300

GnomAD4 genome AF: 0.00353 AC: 538 AN: 152268 Hom.: 4 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74450

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.00362

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00326 Hom.: 1

Bravo AF: 0.00161

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00202

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary North American Indian childhood cirrhosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.18
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs144266389; hg19: chr16-69177169;