4-106325015-AAAT-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001142416.2(AIMP1):c.10_12delAAT(p.Asn4del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,603,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
AIMP1
NM_001142416.2 conservative_inframe_deletion
NM_001142416.2 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.61
Genes affected
AIMP1 (HGNC:10648): (aminoacyl tRNA synthetase complex interacting multifunctional protein 1) The protein encoded by this gene is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. This protein is also involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2008]
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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_001142416.2. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000408 AC: 10AN: 245392Hom.: 0 AF XY: 0.0000377 AC XY: 5AN XY: 132574
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GnomAD4 exome AF: 0.0000207 AC: 30AN: 1451072Hom.: 0 AF XY: 0.0000194 AC XY: 14AN XY: 721260
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74312
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2021 | This variant, c.10_12del, results in the deletion of 1 amino acid(s) of the AIMP1 protein (p.Asn4del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs769350799, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with AIMP1-related conditions. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2023 | In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hypomyelinating leukodystrophy 3 Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 11-10-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at