chrX-123907193-A-G

Position:

chrX-123907193-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001167.4(XIAP):c.*12A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,177,667 control chromosomes in the GnomAD database, including 18,019 homozygotes. There are 81,282 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 1528 hom., 6631 hem., cov: 23)

Exomes 𝑓: 0.21 ( 16491 hom. 74651 hem. )

Consequence

XIAP
NM_001167.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.402

Variant links:

Genes affected

XIAP (HGNC:592): (X-linked inhibitor of apoptosis) This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. Mutations in this gene are the cause of X-linked lymphoproliferative syndrome. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 2 and 11.[provided by RefSeq, Feb 2011]

XIAP links:

XIAP (HGNC:):

XIAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-123907193-A-G is Benign according to our data. Variant chrX-123907193-A-G is described in ClinVar as [Benign]. Clinvar id is 367796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-123907193-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIAP	NM_001167.4 linkuse as main transcript	c.*12A>G		3_prime_UTR_variant	7/7	ENST00000371199.8	NP_001158.2	P98170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIAP	ENST00000371199.8 linkuse as main transcript	c.*12A>G		3_prime_UTR_variant	7/7	1	NM_001167.4	ENSP00000360242.3		P98170

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

21837

AN:

111098

Hom.:

1528

Cov.:

AF XY:

0.199

AC XY:

6619

AN XY:

33318

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.314

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.234

AC:

41172

AN:

175709

Hom.:

3350

AF XY:

0.243

AC XY:

14856

AN XY:

61047

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.211

AC:

225216

AN:

1066516

Hom.:

16491

Cov.:

AF XY:

0.222

AC XY:

74651

AN XY:

335710

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.307

Gnomad4 SAS exome

AF:

0.392

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.197

AC:

21844

AN:

111151

Hom.:

1528

Cov.:

AF XY:

0.199

AC XY:

6631

AN XY:

33381

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.193

Hom.:

1668

Bravo

AF:

0.195

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 22, 2018	- -

X-linked lymphoproliferative disease due to XIAP deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 0

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