rs139407567
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003977.4(AIP):c.807C>A(p.Phe269Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003977.4 missense
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 |
---|---|---|---|---|---|---|---|---|
AIP | NM_003977.4 | c.807C>A | p.Phe269Leu | missense_variant | Exon 6 of 6 | ENST00000279146.8 | NP_003968.3 | |
AIP | NM_001302960.2 | c.799C>A | p.Gln267Lys | missense_variant | Exon 6 of 6 | NP_001289889.1 | ||
AIP | NM_001302959.2 | c.630C>A | p.Phe210Leu | missense_variant | Exon 6 of 6 | NP_001289888.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 269 of the AIP protein (p.Phe269Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AIP-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIP protein function. 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. -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.F269L variant (also known as c.807C>A), located in coding exon 6 of the AIP gene, results from a C to A substitution at nucleotide position 807. The phenylalanine at codon 269 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.