X-123885796-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001167.4(XIAP):c.134C>T(p.Ser45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,210,223 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000026 ( 0 hom. 7 hem. )
Consequence
XIAP
NM_001167.4 missense
NM_001167.4 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 2.14
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.086987734).
BP6
Variant X-123885796-C-T is Benign according to our data. Variant chrX-123885796-C-T is described in ClinVar as [Benign]. Clinvar id is 2146388.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000264 (29/1098209) while in subpopulation AMR AF= 0.000795 (28/35204). AF 95% confidence interval is 0.000565. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XIAP | NM_001167.4 | c.134C>T | p.Ser45Leu | missense_variant | 2/7 | ENST00000371199.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XIAP | ENST00000371199.8 | c.134C>T | p.Ser45Leu | missense_variant | 2/7 | 1 | NM_001167.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 112014Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34196
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GnomAD3 exomes AF: 0.000147 AC: 27AN: 183320Hom.: 0 AF XY: 0.000103 AC XY: 7AN XY: 67884
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GnomAD4 exome AF: 0.0000264 AC: 29AN: 1098209Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 7AN XY: 363563
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GnomAD4 genome AF: 0.0000179 AC: 2AN: 112014Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34196
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked lymphoproliferative disease due to XIAP deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;D;N;N
REVEL
Benign
Sift
Uncertain
D;T;D;D
Sift4G
Benign
T;T;T;T
Polyphen
P;.;P;P
Vest4
MutPred
Loss of disorder (P = 0.0108);Loss of disorder (P = 0.0108);Loss of disorder (P = 0.0108);Loss of disorder (P = 0.0108);
MVP
MPC
0.23
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at