chrX-49880738-A-G

Position:

• chrX-49880738-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145073.3(USP27X):​c.431A>G​(p.Tyr144Cys) 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. 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 P:1 U:1
• Conservation: PhyloP100: 5.26

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38124603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP27X	NM_001145073.3	c.431A>G	p.Tyr144Cys	missense_variant	1/1	ENST00000621775.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP27X	ENST00000621775.2	c.431A>G	p.Tyr144Cys	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: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 105 Pathogenic:1 Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 15, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Hadassah Hebrew University Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	26
DANN	Benign	0.83
DEOGEN2	Benign	0.054	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.38	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.35
MVP		0.26
GERP RS		3.9
Varity_R		0.24
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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-49645341;