X-49880699-G-A

Position:

• chrX-49880699-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145073.3(USP27X):​c.392G>A​(p.Arg131Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: USP27X NM_001145073.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05808592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP27X	NM_001145073.3	c.392G>A	p.Arg131Gln	missense_variant	1/1	ENST00000621775.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP27X	ENST00000621775.2	c.392G>A	p.Arg131Gln	missense_variant	1/1		NM_001145073.3	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.392G>A (p.R131Q) alteration is located in exon 1 (coding exon 1) of the USP27X gene. This alteration results from a G to A substitution at nucleotide position 392, causing the arginine (R) at amino acid position 131 to be replaced by a glutamine (Q). 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	0.094
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0098	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.058	T
MutationAssessor	Benign	-0.43	N
PrimateAI	Benign	0.46	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.081
MVP		0.043
GERP RS		3.9
Varity_R		0.17
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49645302;