chrX-56565256-G-A

Position:

chrX-56565256-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_013444.4(UBQLN2):c.1383G>A(p.Gly461Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,210,925 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,407 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., 127 hem., cov: 23)

Exomes 𝑓: 0.0036 ( 7 hom. 1280 hem. )

Consequence

UBQLN2
NM_013444.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.194

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant X-56565256-G-A is Benign according to our data. Variant chrX-56565256-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-56565256-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.194 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00312 (352/112788) while in subpopulation NFE AF= 0.0031 (165/53236). AF 95% confidence interval is 0.00271. There are 0 homozygotes in gnomad4. There are 127 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 127 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBQLN2	NM_013444.4 linkuse as main transcript	c.1383G>A	p.Gly461Gly	synonymous_variant	1/1	ENST00000338222.7	NP_038472.2	Q9UHD9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBQLN2	ENST00000338222.7 linkuse as main transcript	c.1383G>A	p.Gly461Gly	synonymous_variant	1/1	6	NM_013444.4	ENSP00000345195.5		Q9UHD9

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

352

AN:

112734

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

127

AN XY:

34886

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00306

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000712

Gnomad FIN

AF:

0.0195

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00329

GnomAD3 exomes

AF:

0.00367

AC:

673

AN:

183302

Hom.:

AF XY:

0.00382

AC XY:

259

AN XY:

67752

show subpopulations

Gnomad AFR exome

AF:

0.000533

Gnomad AMR exome

AF:

0.000912

Gnomad ASJ exome

AF:

0.00240

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00356

AC:

3911

AN:

1098137

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

1280

AN XY:

363497

show subpopulations

Gnomad4 AFR exome

AF:

0.000455

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00157

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.00341

Gnomad4 OTH exome

AF:

0.00323

GnomAD4 genome

AF:

0.00312

AC:

352

AN:

112788

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

127

AN XY:

34950

show subpopulations

Gnomad4 AFR

AF:

0.000579

Gnomad4 AMR

AF:

0.00306

Gnomad4 ASJ

AF:

0.00226

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000714

Gnomad4 FIN

AF:

0.0195

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00325

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00238

EpiCase

AF:

0.00485

EpiControl

AF:

0.00421

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 15

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 08, 2021	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 22, 2020

- -

Amyotrophic Lateral Sclerosis, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.7

DANN

Benign

0.60

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