NM_001167.4:c.*4078C>T

Variant names:

• chrX-123911259-C-T
• rs28382751
• NM_001167.4:c.*4078C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001167.4(XIAP):​c.*4078C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000941 in 106,260 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000094 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.0000047 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: XIAP NM_001167.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.*4078C>T		3_prime_UTR	Exon 7 of 7	NP_001158.2
	XIAP	NM_001204401.2		c.*4078C>T		3_prime_UTR	Exon 7 of 7	NP_001191330.1	P98170
	XIAP	NM_001378590.1		c.*4078C>T		3_prime_UTR	Exon 7 of 7	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.*4078C>T		3_prime_UTR	Exon 7 of 7	ENSP00000360242.3	P98170
	XIAP	ENST00000355640.3	TSL:5	c.*4078C>T		3_prime_UTR	Exon 7 of 7	ENSP00000347858.3	P98170

Frequencies

GnomAD3 genomes AF: 0.00000941 AC: 1 AN: 106260 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000290

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000218 AC: 2 AN: 91765 AF XY: 0.0000301

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000260

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000471 AC: 1 AN: 212416 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 83726

African (AFR) AF: 0.00 AC: 0 AN: 5953

American (AMR) AF: 0.00 AC: 0 AN: 21179

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7872

East Asian (EAS) AF: 0.000150 AC: 1 AN: 6658

South Asian (SAS) AF: 0.00 AC: 0 AN: 35372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 114948

Other (OTH) AF: 0.00 AC: 0 AN: 10280

GnomAD4 genome AF: 0.00000941 AC: 1 AN: 106260 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 31532

African (AFR) AF: 0.00 AC: 0 AN: 26875

American (AMR) AF: 0.00 AC: 0 AN: 10160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2632

East Asian (EAS) AF: 0.000290 AC: 1 AN: 3454

South Asian (SAS) AF: 0.00 AC: 0 AN: 2591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52520

Other (OTH) AF: 0.00 AC: 0 AN: 1425

Alfa AF: 0.00 Hom.: 259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.56
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs28382751; hg19: chrX-123045109;