Variant X-133025894-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_031907.3(USP26):c.2327C>T(p.Thr776Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,097,879 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000024 ( 0 hom. 9 hem. )

Consequence

USP26
NM_031907.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.832

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14064586).

BP6

Variant X-133025894-G-A is Benign according to our data. Variant chrX-133025894-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661459.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP26	NM_031907.3 linkuse as main transcript	c.2327C>T	p.Thr776Ile	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.2327C>T	p.Thr776Ile	missense_variant	6/6	2	NM_031907.3	ENSP00000423390.1		Q9BXU7
USP26	ENST00000370832.1 linkuse as main transcript	c.2327C>T	p.Thr776Ile	missense_variant	1/1	6		ENSP00000359869.1		Q9BXU7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000711

AC:

AN:

182771

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

67445

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000476

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000237

AC:

AN:

1097879

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363303

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000683

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

USP26: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.39

.;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.96

D;D

Vest4

0.28

MutPred

0.39

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);

MVP

0.64

MPC

0.32

ClinPred

0.34

GERP RS

2.1

Varity_R

0.23

gMVP

0.11

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