chr12-110218207-AGGACC-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePM2BS1_Supporting
The NM_014055.4(IFT81):c.2015_2019delACCGG(p.Asp672AlafsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,562,968 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014055.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IFT81 | NM_014055.4 | c.2015_2019delACCGG | p.Asp672AlafsTer15 | frameshift_variant | Exon 19 of 19 | ENST00000242591.10 | NP_054774.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000432 AC: 61AN: 1410686Hom.: 1 AF XY: 0.0000458 AC XY: 32AN XY: 699238
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change results in a frameshift in the IFT81 gene (p.Asp672Alafs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the IFT81 protein and extend the protein by 9 additional amino acid residues. This variant is present in population databases (rs763354429, gnomAD 0.04%). This frameshift has been observed in individual(s) with retinal disease and intellectual disability (PMID: 26275418). ClinVar contains an entry for this variant (Variation ID: 218893). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on IFT81 function (PMID: 26275418). 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. -
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Ciliopathy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at