Variant 1-229634943-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014777.4(URB2):c.330C>A(p.Phe110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000748 in 1,536,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

URB2
NM_014777.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.245

Variant links:

Genes affected

URB2 (HGNC:28967): (URB2 ribosome biogenesis homolog) Predicted to be involved in ribosome biogenesis. Located in aggresome; midbody; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

URB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07342848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
URB2	NM_014777.4 linkuse as main transcript	c.330C>A	p.Phe110Leu	missense_variant	4/10	ENST00000258243.7	NP_055592.2
URB2	NM_001314021.2 linkuse as main transcript	c.330C>A	p.Phe110Leu	missense_variant	4/10		NP_001300950.1
URB2	XM_005273360.3 linkuse as main transcript	c.330C>A	p.Phe110Leu	missense_variant	4/9		XP_005273417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
URB2	ENST00000258243.7 linkuse as main transcript	c.330C>A	p.Phe110Leu	missense_variant	4/10	1	NM_014777.4	ENSP00000258243	P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152126

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000508

AC:

AN:

196738

Hom.:

AF XY:

0.0000286

AC XY:

AN XY:

105032

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000751

AC:

104

AN:

1384340

Hom.:

Cov.:

AF XY:

0.0000662

AC XY:

AN XY:

680212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000326

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:

0.0000922

Gnomad4 OTH exome

AF:

0.0000703

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74304

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:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000495

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.330C>A (p.F110L) alteration is located in exon 4 (coding exon 3) of the URB2 gene. This alteration results from a C to A substitution at nucleotide position 330, causing the phenylalanine (F) at amino acid position 110 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.56

M_CAP

Benign

0.0063

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.6

REVEL

Benign

0.014

Sift

Benign

0.29

Sift4G

Benign

0.089

Polyphen

0.076

Vest4

0.064

MutPred

0.26

Loss of catalytic residue at F110 (P = 0.0584);

MVP

0.072

MPC

0.10

ClinPred

0.052

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.16

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over