chrX-123900377-A-G

Variant names:

• chrX-123900377-A-G
• rs5958338
• NM_001167.4:c.1100-116A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001167.4(XIAP):​c.1100-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (13383 hom., 19178 hem., cov: 23)
  • Exomes 𝑓: 0.57 (65243 hom. 91629 hem.)
  • Failed GnomAD Quality Control
• Consequence: XIAP NM_001167.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.186
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• X-linked lymphoproliferative disease due to XIAP deficiency

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-123900377-A-G is Benign according to our data. Variant chrX-123900377-A-G is described in ClinVar as Benign. ClinVar VariationId is 1178358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIAP	NM_001167.4	MANE Select	c.1100-116A>G		intron	N/A	NP_001158.2
	XIAP	NM_001204401.2		c.1100-116A>G		intron	N/A	NP_001191330.1	P98170
	XIAP	NM_001378590.1		c.1100-116A>G		intron	N/A	NP_001365519.1	P98170

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIAP	ENST00000371199.8	TSL:1 MANE Select	c.1100-116A>G		intron	N/A	ENSP00000360242.3	P98170
	XIAP	ENST00000497640.1	TSL:1	n.322-116A>G		intron	N/A
	XIAP	ENST00000355640.3	TSL:5	c.1100-116A>G		intron	N/A	ENSP00000347858.3	P98170

Frequencies

GnomAD3 genomes AF: 0.584 AC: 64594 AN: 110531 Hom.: 13383 Cov.: 23

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.581

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.571 AC: 318451 AN: 557912 Hom.: 65243 AF XY: 0.578 AC XY: 91629 AN XY: 158594

African (AFR) AF: 0.641 AC: 8986 AN: 14012

American (AMR) AF: 0.561 AC: 10453 AN: 18628

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 7174 AN: 13340

East Asian (EAS) AF: 0.367 AC: 9000 AN: 24495

South Asian (SAS) AF: 0.596 AC: 19712 AN: 33069

European-Finnish (FIN) AF: 0.652 AC: 22799 AN: 34957

Middle Eastern (MID) AF: 0.577 AC: 1025 AN: 1776

European-Non Finnish (NFE) AF: 0.573 AC: 223503 AN: 390233

Other (OTH) AF: 0.577 AC: 15799 AN: 27402

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.585 AC: 64636 AN: 110580 Hom.: 13383 Cov.: 23 AF XY: 0.584 AC XY: 19178 AN XY: 32858

African (AFR) AF: 0.637 AC: 19378 AN: 30438

American (AMR) AF: 0.582 AC: 5999 AN: 10312

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1405 AN: 2629

East Asian (EAS) AF: 0.423 AC: 1486 AN: 3512

South Asian (SAS) AF: 0.566 AC: 1519 AN: 2684

European-Finnish (FIN) AF: 0.661 AC: 3795 AN: 5741

Middle Eastern (MID) AF: 0.606 AC: 131 AN: 216

European-Non Finnish (NFE) AF: 0.563 AC: 29755 AN: 52872

Other (OTH) AF: 0.583 AC: 881 AN: 1512

Alfa AF: 0.573 Hom.: 4407

Bravo AF: 0.584

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5958338; hg19: chrX-123034227; COSMIC: COSV63024519;