rs1555871928
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_000383.4(AIRE):c.319_321delinsTG(p.Ser107CysfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
AIRE
NM_000383.4 frameshift
NM_000383.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.92
Genes affected
AIRE (HGNC:360): (autoimmune regulator) This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 21-44286989-AGC-TG is Pathogenic according to our data. Variant chr21-44286989-AGC-TG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 557904.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIRE | NM_000383.4 | c.319_321delinsTG | p.Ser107CysfsTer40 | frameshift_variant | 3/14 | ENST00000291582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIRE | ENST00000291582.6 | c.319_321delinsTG | p.Ser107CysfsTer40 | frameshift_variant | 3/14 | 1 | NM_000383.4 | P1 | |
AIRE | ENST00000527919.5 | n.480_482delinsTG | non_coding_transcript_exon_variant | 3/14 | 2 | ||||
AIRE | ENST00000530812.5 | n.488_490delinsTG | non_coding_transcript_exon_variant | 3/12 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Polyglandular autoimmune syndrome, type 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 17, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at