Variant X-133026287-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031907.3(USP26):c.1934A>G(p.Asp645Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,693 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.0000064 ( 0 hom. 6 hem. )

Consequence

USP26
NM_031907.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00400

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14850366).

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP26	NM_031907.3 linkuse as main transcript	c.1934A>G	p.Asp645Gly	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.1934A>G	p.Asp645Gly	missense_variant	6/6	2	NM_031907.3	ENSP00000423390.1		Q9BXU7
USP26	ENST00000370832.1 linkuse as main transcript	c.1934A>G	p.Asp645Gly	missense_variant	1/1	6		ENSP00000359869.1		Q9BXU7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182558

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097693

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363165

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.1934A>G (p.D645G) alteration is located in exon 1 (coding exon 1) of the USP26 gene. This alteration results from a A to G substitution at nucleotide position 1934, causing the aspartic acid (D) at amino acid position 645 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.036

T;T

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.37

.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.17

Sift

Benign

0.63

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.91

P;P

Vest4

0.045

MutPred

0.54

Loss of solvent accessibility (P = 0.0231);Loss of solvent accessibility (P = 0.0231);

MVP

0.51

MPC

0.16

ClinPred

0.28

GERP RS

0.91

Varity_R

0.21

gMVP

0.068

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