rs146724128

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013438.5(UBQLN1):c.1064G>T(p.Gly355Val) variant causes a missense change. The variant allele was found at a frequency of 0.00595 in 1,614,118 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 33 hom. )

Consequence

UBQLN1
NM_013438.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.97

Publications

11 publications found

Variant links:

Genes affected

UBQLN1 (HGNC:12508): (ubiquilin 1) This gene encodes an ubiquitin-like protein (ubiquilin) that shares a high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain an 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 modulate accumulation of presenilin proteins, and it is found in lesions associated with Alzheimer's and Parkinson's disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UBQLN1 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

UBQLN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00836888).

BP6

Variant 9-83677768-C-A is Benign according to our data. Variant chr9-83677768-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 775275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00601 (8793/1461882) while in subpopulation MID AF = 0.0191 (110/5768). AF 95% confidence interval is 0.0162. There are 33 homozygotes in GnomAdExome4. There are 4309 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 803 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013438.5. 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
	UBQLN1	NM_013438.5	MANE Select	c.1064G>T	p.Gly355Val	missense	Exon 6 of 11	NP_038466.2
	UBQLN1	NM_053067.3		c.1064G>T	p.Gly355Val	missense	Exon 6 of 10	NP_444295.1	Q9UMX0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBQLN1	ENST00000376395.9	TSL:1 MANE Select	c.1064G>T	p.Gly355Val	missense	Exon 6 of 11	ENSP00000365576.4	Q9UMX0-1
UBQLN1	ENST00000257468.11	TSL:1	c.1064G>T	p.Gly355Val	missense	Exon 6 of 10	ENSP00000257468.7	Q9UMX0-2
UBQLN1	ENST00000533705.5	TSL:1	n.782G>T		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

803

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00748

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00491

AC:

1234

AN:

251326

AF XY:

0.00485

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00503

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.00787

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00601

AC:

8793

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

4309

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33480

American (AMR)

AF:

0.00539

AC:

241

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00398

AC:

104

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000626

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00307

AC:

164

AN:

53420

Middle Eastern (MID)

AF:

0.0191

AC:

110

AN:

5768

European-Non Finnish (NFE)

AF:

0.00695

AC:

7732

AN:

1112002

Other (OTH)

AF:

0.00571

AC:

345

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

464

927

1391

1854

2318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.00527

AC:

803

AN:

152236

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

417

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41534

American (AMR)

AF:

0.0104

AC:

159

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00748

AC:

509

AN:

68020

Other (OTH)

AF:

0.0137

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

113

150

188

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:

0.00634

Hom.:

Bravo

AF:

0.00540

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00524

AC:

636

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00752

EpiControl

AF:

0.00830

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.0084

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.7

PhyloP100

5.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.46

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.77

MVP

0.94

MPC

0.99

ClinPred

0.048

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.66

Mutation Taster

=89/11

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over