9-83677768-C-A

Position:

chr9-83677768-C-A

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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. gnomad4_exome 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 gnomad4_exome. There are 4309 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 803 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UBQLN1	NM_013438.5 linkuse as main transcript	c.1064G>T	p.Gly355Val	missense_variant	6/11	ENST00000376395.9
UBQLN1	NM_053067.3 linkuse as main transcript	c.1064G>T	p.Gly355Val	missense_variant	6/10
UBQLN1	XM_005251948.4 linkuse as main transcript	c.1064G>T	p.Gly355Val	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBQLN1	ENST00000376395.9 linkuse as main transcript	c.1064G>T	p.Gly355Val	missense_variant	6/11	1	NM_013438.5	P3	Q9UMX0-1
UBQLN1	ENST00000257468.11 linkuse as main transcript	c.1064G>T	p.Gly355Val	missense_variant	6/10	1		A1	Q9UMX0-2
UBQLN1	ENST00000533705.5 linkuse as main transcript	n.782G>T		non_coding_transcript_exon_variant	5/9	1
UBQLN1	ENST00000529923.1 linkuse as main transcript	c.455G>T	p.Gly152Val	missense_variant	3/3	2

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

GnomAD3 exomes

AF:

0.00491

AC:

1234

AN:

251326

Hom.:

AF XY:

0.00485

AC XY:

659

AN XY:

135830

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 SAS exome

AF:

0.000621

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

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.00307

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.00527

AC:

803

AN:

152236

Hom.:

Cov.:

AF XY:

0.00560

AC XY:

417

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00748

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00675

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

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	UBQLN1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.7

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.4

N;N;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

1.0

D;P;.

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

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