Variant 11-5515895-G-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_145053.5(UBQLNL):c.547C>T(p.Arg183Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,613,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

UBQLNL
NM_145053.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.424

Variant links:

Genes affected

UBQLNL (HGNC:28294): (ubiquilin like) Predicted to enable polyubiquitin modification-dependent protein binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

UBQLNL 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=0.13004825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBQLNL	NM_145053.5 linkuse as main transcript	c.547C>T	p.Arg183Trp	missense_variant	1/1	ENST00000380184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBQLNL	ENST00000380184.2 linkuse as main transcript	c.547C>T	p.Arg183Trp	missense_variant	1/1		NM_145053.5	A2	Q8IYU4-1
UBQLNL	ENST00000673910.1 linkuse as main transcript	c.517C>T	p.Arg173Trp	missense_variant	2/2			P4

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000108

AC:

AN:

249494

Hom.:

AF XY:

0.0000964

AC XY:

AN XY:

134854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000261

AC:

381

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000321

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000112

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

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

Aug 06, 2021

The c.547C>T (p.R183W) alteration is located in exon 1 (coding exon 1) of the UBQLNL gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a tryptophan (W). 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

Benign

0.082

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.58

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.56

M_CAP

Benign

0.0051

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.018

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.014

Polyphen

0.029

Vest4

0.17

MVP

0.25

MPC

0.015

ClinPred

0.11

GERP RS

1.9

Varity_R

0.052

gMVP

0.22

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