rs777303823
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001167.4(XIAP):c.844G>A(p.Glu282Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,203,165 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E282Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001167.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XIAP | NM_001167.4 | c.844G>A | p.Glu282Lys | missense_variant | 2/7 | ENST00000371199.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XIAP | ENST00000371199.8 | c.844G>A | p.Glu282Lys | missense_variant | 2/7 | 1 | NM_001167.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000107 AC: 12AN: 111686Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33880
GnomAD3 exomes AF: 0.0000339 AC: 6AN: 177168Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 65302
GnomAD4 exome AF: 0.00000825 AC: 9AN: 1091479Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 360797
GnomAD4 genome AF: 0.000107 AC: 12AN: 111686Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33880
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 18, 2016 | - - |
X-linked lymphoproliferative disease due to XIAP deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 282 of the XIAP protein (p.Glu282Lys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 287381). This variant has not been reported in the literature in individuals affected with XIAP-related conditions. This variant is present in population databases (rs777303823, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. - |
Autoinflammatory syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
X-linked lymphoproliferative disease due to XIAP deficiency;C5399825:X-linked lymphoproliferative disease due to SH2D1A deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at