5-14664896-AGGC-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_138348.6(OTULIN):βc.78_80delβ(p.Ala27del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,169,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.0000070 ( 0 hom., cov: 34)
Exomes π: 9.7e-7 ( 0 hom. )
Consequence
OTULIN
NM_138348.6 inframe_deletion
NM_138348.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.09
Genes affected
OTULIN (HGNC:25118): (OTU deubiquitinase with linear linkage specificity) This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_138348.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTULIN | NM_138348.6 | c.78_80del | p.Ala27del | inframe_deletion | 1/7 | ENST00000284274.5 | NP_612357.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTULIN | ENST00000284274.5 | c.78_80del | p.Ala27del | inframe_deletion | 1/7 | 1 | NM_138348.6 | ENSP00000284274 | P1 | |
OTULIN | ENST00000507335.1 | n.172_174del | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
OTULIN | ENST00000503023.2 | c.78_80del | p.Ala27del | inframe_deletion, NMD_transcript_variant | 1/6 | 5 | ENSP00000427016 | |||
OTULIN | ENST00000697367.1 | c.78_80del | p.Ala27del | inframe_deletion, NMD_transcript_variant | 1/5 | ENSP00000513279 |
Frequencies
GnomAD3 genomes AF: 0.00000702 AC: 1AN: 142356Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 9.74e-7 AC: 1AN: 1026770Hom.: 0 AF XY: 0.00000206 AC XY: 1AN XY: 484722
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GnomAD4 genome AF: 0.00000702 AC: 1AN: 142356Hom.: 0 Cov.: 34 AF XY: 0.0000144 AC XY: 1AN XY: 69682
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 13, 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with OTULIN-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.78_80del, results in the deletion of 1 amino acid(s) of the OTULIN protein (p.Ala27del), but otherwise preserves the integrity of the reading frame. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at