chrX-123906813-T-C

Position:

• chrX-123906813-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167.4(XIAP):​c.1301-175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 111,423 control chromosomes in the GnomAD database, including 1,486 homozygotes. There are 6,692 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (1486 hom., 6692 hem., cov: 23)
• Consequence: XIAP NM_001167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIAP	NM_001167.4	c.1301-175T>C		intron_variant		ENST00000371199.8	NP_001158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIAP	ENST00000371199.8	c.1301-175T>C		intron_variant		1	NM_001167.4	ENSP00000360242.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 21593 AN: 111369 Hom.: 1486 Cov.: 23 AF XY: 0.199 AC XY: 6681 AN XY: 33601

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 21599 AN: 111423 Hom.: 1486 Cov.: 23 AF XY: 0.199 AC XY: 6692 AN XY: 33665

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.206

Alfa AF: 0.0579 Hom.: 259

Bravo AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.70

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: rs17334739; hg19: chrX-123040663;