Variant X-133026128-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031907.3(USP26):c.2093G>A(p.Arg698Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,208,457 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

USP26
NM_031907.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017509967).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP26	NM_031907.3 linkuse as main transcript	c.2093G>A	p.Arg698Gln	missense_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.2093G>A	p.Arg698Gln	missense_variant	6/6	2	NM_031907.3	ENSP00000423390.1		Q9BXU7
USP26	ENST00000370832.1 linkuse as main transcript	c.2093G>A	p.Arg698Gln	missense_variant	1/1	6		ENSP00000359869.1		Q9BXU7

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110476

Hom.:

Cov.:

AF XY:

0.0000612

AC XY:

AN XY:

32706

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000973

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000288

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182482

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67532

show subpopulations

Gnomad AFR exome

AF:

0.0000778

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097924

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363330

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110533

Hom.:

Cov.:

AF XY:

0.0000610

AC XY:

AN XY:

32773

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000972

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000289

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0020

DANN

Benign

0.66

DEOGEN2

Benign

0.00086

T;T

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.38

.;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.49

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.28

N;N

REVEL

Benign

0.014

Sift

Benign

0.58

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.013

B;B

Vest4

0.061

MutPred

0.40

Loss of MoRF binding (P = 0.0451);Loss of MoRF binding (P = 0.0451);

MVP

0.60

MPC

0.066

ClinPred

0.034

GERP RS

-8.3

Varity_R

0.023

gMVP

0.051

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