Genetic Variant XIAP:c.*80G>T (chrX-123907261-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001167.4(XIAP):c.*80G>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 0.0000164 in 915,611 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 2 hem. )

Consequence

XIAP
NM_001167.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

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>T	3_prime_UTR	Exon 7 of 7	NP_001158.2
XIAP	NM_001204401.2		c.*80G>T	3_prime_UTR	Exon 7 of 7	NP_001191330.1	P98170
XIAP	NM_001378590.1		c.*80G>T	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>T	3_prime_UTR	Exon 7 of 7	ENSP00000360242.3	P98170
XIAP	ENST00000355640.3	TSL:5	c.*80G>T	3_prime_UTR	Exon 7 of 7	ENSP00000347858.3	P98170
XIAP	ENST00000422098.6	TSL:4	c.*80G>T	3_prime_UTR	Exon 9 of 9	ENSP00000405529.2	P98170

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111551

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

132506

AF XY:

0.0000243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000468

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000559

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

804060

Hom.:

Cov.:

AF XY:

0.00000941

AC XY:

AN XY:

212466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20340

American (AMR)

AF:

0.0000335

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:

0.0000188

AC:

AN:

586092

Other (OTH)

AF:

0.00

AC:

AN:

36231

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0000269

AC:

AN:

111551

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33759

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30765

American (AMR)

AF:

0.00

AC:

AN:

10405

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3581

South Asian (SAS)

AF:

0.00

AC:

AN:

2744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53088

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

301

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.72

PhyloP100

0.053

Mutation Taster

=100/0

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over