rs12838858

Variant names:

• chrX-123907261-G-A
• rs12838858
• NM_001167.4:c.*80G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-123907261-G-A
• chrX-123907261-G-C
• chrX-123907261-G-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.*80G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 804,060 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: XIAP NM_001167.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae)

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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XIAP	NM_001167.4	c.*80G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000371199.8	NP_001158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XIAP	ENST00000371199.8	c.*80G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001167.4	ENSP00000360242.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000124 AC: 1 AN: 804060 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 212466

African (AFR) AF: 0.00 AC: 0 AN: 20340

American (AMR) AF: 0.00 AC: 0 AN: 29824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17241

East Asian (EAS) AF: 0.00 AC: 0 AN: 27382

South Asian (SAS) AF: 0.00 AC: 0 AN: 45226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3252

European-Non Finnish (NFE) AF: 0.00000171 AC: 1 AN: 586092

Other (OTH) AF: 0.00 AC: 0 AN: 36231

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.67
PhyloP100		0.053

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: rs12838858; hg19: chrX-123041111;