rs45559331

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_013444.4(UBQLN2):c.1461C>A(p.Thr487Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00771 in 1,208,008 control chromosomes in the GnomAD database, including 44 homozygotes. There are 2,959 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., 183 hem., cov: 23)

Exomes 𝑓: 0.0079 ( 37 hom. 2776 hem. )

Consequence

UBQLN2
NM_013444.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:10

Conservation

PhyloP100: -2.79

Publications

3 publications found

Variant links:

Genes affected

UBQLN2 (HGNC:12509): (ubiquilin 2) This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases; and thus, are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein. [provided by RefSeq, Oct 2009]

UBQLN2 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 15
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

UBQLN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant X-56565334-C-A is Benign according to our data. Variant chrX-56565334-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 260311.

BP7

Synonymous conserved (PhyloP=-2.79 with no splicing effect.

BS2

High AC in GnomAd4 at 674 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLN2	NM_013444.4 link	c.1461C>A	p.Thr487Thr	synonymous_variant	Exon 1 of 1	ENST00000338222.7	NP_038472.2	Q9UHD9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLN2	ENST00000338222.7 link	c.1461C>A	p.Thr487Thr	synonymous_variant	Exon 1 of 1	6	NM_013444.4	ENSP00000345195.5		Q9UHD9

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

675

AN:

112340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00830

Gnomad ASJ

AF:

0.00866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00109

Gnomad FIN

AF:

0.00341

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00901

Gnomad OTH

AF:

0.00989

GnomAD2 exomes

AF:

0.00595

AC:

1041

AN:

174861

AF XY:

0.00573

show subpopulations

Gnomad AFR exome

AF:

0.00121

Gnomad AMR exome

AF:

0.00369

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00463

Gnomad NFE exome

AF:

0.00903

Gnomad OTH exome

AF:

0.00805

GnomAD4 exome

AF:

0.00789

AC:

8641

AN:

1095615

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

2776

AN XY:

361221

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

26350

American (AMR)

AF:

0.00421

AC:

147

AN:

34911

Ashkenazi Jewish (ASJ)

AF:

0.0125

AC:

241

AN:

19336

East Asian (EAS)

AF:

0.00

AC:

AN:

30106

South Asian (SAS)

AF:

0.00138

AC:

AN:

53763

European-Finnish (FIN)

AF:

0.00461

AC:

186

AN:

40314

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

4123

European-Non Finnish (NFE)

AF:

0.00899

AC:

7560

AN:

840723

Other (OTH)

AF:

0.00774

AC:

356

AN:

45989

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

405

810

1216

1621

2026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00600

AC:

674

AN:

112393

Hom.:

Cov.:

AF XY:

0.00530

AC XY:

183

AN XY:

34559

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

30985

American (AMR)

AF:

0.00829

AC:

AN:

10732

Ashkenazi Jewish (ASJ)

AF:

0.00866

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3536

South Asian (SAS)

AF:

0.00109

AC:

AN:

2756

European-Finnish (FIN)

AF:

0.00341

AC:

AN:

6153

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00901

AC:

479

AN:

53135

Other (OTH)

AF:

0.00977

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00634

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:4

Apr 01, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 25, 2020

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Uncertain:1Benign:2

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 02, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amyotrophic lateral sclerosis type 15

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 06, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.6

(source)

DANN

Benign

0.71

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over