21-44286019-GC-TT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000383.4(AIRE):c.13_14delGCinsTT(p.Ala5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000383.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AIRE | ENST00000291582.6 | c.13_14delGCinsTT | p.Ala5Leu | missense_variant | 1 | NM_000383.4 | ENSP00000291582.5 | |||
AIRE | ENST00000527919.5 | n.174_175delGCinsTT | non_coding_transcript_exon_variant | Exon 1 of 14 | 2 | |||||
AIRE | ENST00000530812.5 | n.182_183delGCinsTT | non_coding_transcript_exon_variant | Exon 1 of 12 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Polyglandular autoimmune syndrome, type 1 Uncertain:1
This sequence change replaces alanine with leucine at codon 5 of the AIRE protein (p.Ala5Leu). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with AIRE-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.