rs16958656

Variant names:

• chr16-69136806-G-A
• rs16958656
• NM_032830.3:c.270G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-69136806-G-A
• chr16-69136806-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032830.3(UTP4):​c.270G>A​(p.Ala90Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,140 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (8 hom.)
• Consequence: UTP4 NM_032830.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.184
• Publications: 2 publications found

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: Orphanet, G2P
• cirrhosis, familial

  Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-69136806-G-A is Benign according to our data. Variant chr16-69136806-G-A is described in ClinVar as Benign. ClinVar VariationId is 887042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.184 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 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.270G>A	p.Ala90Ala	synonymous	Exon 3 of 17	NP_116219.2	Q969X6-1
	UTP4	NM_001318391.2		c.21G>A	p.Ala7Ala	synonymous	Exon 3 of 17	NP_001305320.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP4	ENST00000314423.12	TSL:1 MANE Select	c.270G>A	p.Ala90Ala	synonymous	Exon 3 of 17	ENSP00000327179.7	Q969X6-1
	UTP4	ENST00000562237.5	TSL:1	c.312G>A	p.Ala104Ala	synonymous	Exon 3 of 17	ENSP00000456709.1	H3BSH7
	UTP4	ENST00000960037.1		c.270G>A	p.Ala90Ala	synonymous	Exon 3 of 17	ENSP00000630096.1

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 698 AN: 152176 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.000500

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00143 AC: 359 AN: 251496 AF XY: 0.000964

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000360

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000889 AC: 1300 AN: 1461846 Hom.: 8 Cov.: 32 AF XY: 0.000804 AC XY: 585 AN XY: 727220

African (AFR) AF: 0.0144 AC: 482 AN: 33478

American (AMR) AF: 0.00105 AC: 47 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000627 AC: 697 AN: 1111978

Other (OTH) AF: 0.00106 AC: 64 AN: 60392

GnomAD4 genome AF: 0.00460 AC: 700 AN: 152294 Hom.: 4 Cov.: 32 AF XY: 0.00415 AC XY: 309 AN XY: 74456

African (AFR) AF: 0.0153 AC: 634 AN: 41564

American (AMR) AF: 0.00131 AC: 20 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68030

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00240 Hom.: 4

Bravo AF: 0.00498

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary North American Indian childhood cirrhosis (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs16958656; hg19: chr16-69170709;