X-49880515-A-G

Position:

• chrX-49880515-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001145073.3(USP27X):​c.208A>G​(p.Thr70Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000949 in 1,054,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000095 (0 hom. 8 hem.)
• Consequence: USP27X NM_001145073.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040178657).
• BP6: Variant X-49880515-A-G is Benign according to our data. Variant chrX-49880515-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3239423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP27X	NM_001145073.3	c.208A>G	p.Thr70Ala	missense_variant	1/1	ENST00000621775.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP27X	ENST00000621775.2	c.208A>G	p.Thr70Ala	missense_variant	1/1		NM_001145073.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000261 AC: 3 AN: 114943 Hom.: 0 AF XY: 0.0000728 AC XY: 3 AN XY: 41207

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: 0.000211

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000949 AC: 10 AN: 1054201 Hom.: 0 Cov.: 31 AF XY: 0.0000232 AC XY: 8 AN XY: 344941

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: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000676

GnomAD4 genome Cov.: 24

ExAC AF: 0.0000423 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

USP27X: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.8
DANN	Benign	0.68
DEOGEN2	Benign	0.046	T
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.040	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.45	T
Polyphen		0.017	B
Vest4		0.024
MVP		0.043
GERP RS		-4.2
Varity_R		0.058
gMVP		0.72

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

Other links and lift over

dbSNP: rs782027058; hg19: chrX-49645118;