Variant X-133026133-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_031907.3(USP26):c.2088A>G(p.Pro696Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,208,748 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,721 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., 80 hem., cov: 21)

Exomes 𝑓: 0.0046 ( 10 hom. 1641 hem. )

Consequence

USP26
NM_031907.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0390

Variant links:

Genes affected

USP26 (HGNC:13485): (ubiquitin specific peptidase 26) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases and is a deubiquitinating enzyme (DUB) with His and Cys domains. It is specifically expressed in testis tissue. Mutations in this gene have been associated with Sertoli cell-only syndrome and male infertility. [provided by RefSeq, Jul 2008]

USP26 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-133026133-T-C is Benign according to our data. Variant chrX-133026133-T-C is described in ClinVar as [Benign]. Clinvar id is 771230.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 80 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP26	NM_031907.3 linkuse as main transcript	c.2088A>G	p.Pro696Pro	synonymous_variant	6/6	ENST00000511190.6	NP_114113.1	Q9BXU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP26	ENST00000511190.6 linkuse as main transcript	c.2088A>G	p.Pro696Pro	synonymous_variant	6/6	2	NM_031907.3	ENSP00000423390.1		Q9BXU7
USP26	ENST00000370832.1 linkuse as main transcript	c.2088A>G	p.Pro696Pro	synonymous_variant	1/1	6		ENSP00000359869.1		Q9BXU7

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

307

AN:

110692

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

AN XY:

32898

show subpopulations

Gnomad AFR

AF:

0.000689

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00175

Gnomad ASJ

AF:

0.00266

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00232

Gnomad FIN

AF:

0.000171

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00474

Gnomad OTH

AF:

0.00202

GnomAD3 exomes

AF:

0.00306

AC:

558

AN:

182566

Hom.:

AF XY:

0.00332

AC XY:

224

AN XY:

67550

show subpopulations

Gnomad AFR exome

AF:

0.000853

Gnomad AMR exome

AF:

0.00135

Gnomad ASJ exome

AF:

0.00375

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00204

Gnomad FIN exome

AF:

0.000940

Gnomad NFE exome

AF:

0.00506

Gnomad OTH exome

AF:

0.00357

GnomAD4 exome

AF:

0.00456

AC:

5012

AN:

1098001

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

1641

AN XY:

363409

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.00320

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00190

Gnomad4 FIN exome

AF:

0.000815

Gnomad4 NFE exome

AF:

0.00537

Gnomad4 OTH exome

AF:

0.00401

GnomAD4 genome

AF:

0.00278

AC:

308

AN:

110747

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

AN XY:

32963

show subpopulations

Gnomad4 AFR

AF:

0.000687

Gnomad4 AMR

AF:

0.00184

Gnomad4 ASJ

AF:

0.00266

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00233

Gnomad4 FIN

AF:

0.000171

Gnomad4 NFE

AF:

0.00474

Gnomad4 OTH

AF:

0.00199

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.00297

EpiCase

AF:

0.00507

EpiControl

AF:

0.00439

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

USP26-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.7

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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