Variant X-49880419-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_001145073.3(USP27X):c.112T>C(p.Cys38Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,166,586 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. 9/15 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., 1 hem., cov: 24)

Exomes 𝑓: 0.000023 ( 0 hom. 8 hem. )

Consequence

USP27X
NM_001145073.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

Variant links:

Genes affected

USP27X (HGNC:13486): (ubiquitin specific peptidase 27 X-linked) This gene encodes a member of the peptidase protein family. The encoded protein functions as a deubiquitinase that is involved in upregulation of the pro-apoptotic Bim protein. This protein may act as a tumor suppressor by increasing levels of Bim to counteract anti-apoptotic signals in cancer cells. Mutations in this gene have been associated with X-linked cognitive disability. [provided by RefSeq, Dec 2016]

USP27X links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15216145).

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP27X	NM_001145073.3 linkuse as main transcript	c.112T>C	p.Cys38Arg	missense_variant	1/1	ENST00000621775.2	NP_001138545.1	A6NNY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP27X	ENST00000621775.2 linkuse as main transcript	c.112T>C	p.Cys38Arg	missense_variant	1/1	6	NM_001145073.3	ENSP00000483631.1		A6NNY8

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112469

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34625

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000348

AC:

AN:

114904

Hom.:

AF XY:

0.0000727

AC XY:

AN XY:

41276

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000676

Gnomad OTH exome

AF:

0.000306

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1054117

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

344885

show subpopulations

Gnomad4 AFR exome

AF:

0.0000401

Gnomad4 AMR exome

AF:

0.0000717

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:

0.0000244

Gnomad4 OTH exome

AF:

0.0000225

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112469

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34625

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2024

The c.112T>C (p.C38R) alteration is located in exon 1 (coding exon 1) of the USP27X gene. This alteration results from a T to C substitution at nucleotide position 112, causing the cysteine (C) at amino acid position 38 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.022

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.55

M_CAP

Benign

0.055

MetaRNN

Benign

0.15

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.69

Sift4G

Benign

0.39

Polyphen

0.12

Vest4

0.49

MVP

0.16

GERP RS

5.0

Varity_R

0.78

gMVP

0.73

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