chr16-85903083-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_002163.4(IRF8):āc.68A>Gā(p.Tyr23Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y23H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002163.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF8 | NM_002163.4 | c.68A>G | p.Tyr23Cys | missense_variant | 2/9 | ENST00000268638.10 | |
IRF8 | NM_001363907.1 | c.98A>G | p.Tyr33Cys | missense_variant | 2/9 | ||
IRF8 | XM_047434052.1 | c.98A>G | p.Tyr33Cys | missense_variant | 3/10 | ||
IRF8 | NM_001363908.1 | c.-439A>G | 5_prime_UTR_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF8 | ENST00000268638.10 | c.68A>G | p.Tyr23Cys | missense_variant | 2/9 | 1 | NM_002163.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727232
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency;C4016741:Immunodeficiency 32B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IRF8 protein function. ClinVar contains an entry for this variant (Variation ID: 1061796). This variant has not been reported in the literature in individuals affected with IRF8-related conditions. This variant is present in population databases (rs370086181, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 23 of the IRF8 protein (p.Tyr23Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at