4-106327487-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001142416.2(AIMP1):c.146G>A(p.Arg49Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,612,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
AIMP1
NM_001142416.2 missense
NM_001142416.2 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 4.12
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.13910982).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIMP1 | NM_001142416.2 | c.146G>A | p.Arg49Gln | missense_variant | 3/7 | ENST00000672341.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIMP1 | ENST00000672341.1 | c.146G>A | p.Arg49Gln | missense_variant | 3/7 | NM_001142416.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251180Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135810
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460606Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726650
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2024 | The c.146G>A (p.R49Q) alteration is located in exon 3 (coding exon 2) of the AIMP1 gene. This alteration results from a G to A substitution at nucleotide position 146, causing the arginine (R) at amino acid position 49 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | This variant has not been reported in the literature in individuals affected with AIMP1-related conditions. This variant is present in population databases (rs747675209, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 49 of the AIMP1 protein (p.Arg49Gln). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.062
.;B;B;.
Vest4
0.14, 0.14, 0.20
MutPred
Gain of ubiquitination at K46 (P = 0.0212);Gain of ubiquitination at K46 (P = 0.0212);Gain of ubiquitination at K46 (P = 0.0212);.;
MVP
MPC
0.028
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at