Genetic Variant XIAP:c.*80G>A (chrX-123907261-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

Publications

0 publications found

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 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

XIAP links:

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ACMG classification

Classification was made for transcript

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).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XIAP	NM_001167.4	MANE Select	c.*80G>A	3_prime_UTR	Exon 7 of 7	NP_001158.2
XIAP	NM_001204401.2		c.*80G>A	3_prime_UTR	Exon 7 of 7	NP_001191330.1	P98170
XIAP	NM_001378590.1		c.*80G>A	3_prime_UTR	Exon 7 of 7	NP_001365519.1	P98170

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XIAP	ENST00000371199.8	TSL:1 MANE Select	c.*80G>A	3_prime_UTR	Exon 7 of 7	ENSP00000360242.3	P98170
XIAP	ENST00000355640.3	TSL:5	c.*80G>A	3_prime_UTR	Exon 7 of 7	ENSP00000347858.3	P98170
XIAP	ENST00000422098.6	TSL:4	c.*80G>A	3_prime_UTR	Exon 9 of 9	ENSP00000405529.2	P98170

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000124

AC:

AN:

804060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

212466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20340

American (AMR)

AF:

0.00

AC:

AN:

29824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17241

East Asian (EAS)

AF:

0.00

AC:

AN:

27382

South Asian (SAS)

AF:

0.00

AC:

AN:

45226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3252

European-Non Finnish (NFE)

AF:

0.00000171

AC:

AN:

586092

Other (OTH)

AF:

0.00

AC:

AN:

36231

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.0

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over