chr7-6009450-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006303.4(AIMP2):c.87C>G(p.Asn29Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000021 ( 0 hom. )
Consequence
AIMP2
NM_006303.4 missense
NM_006303.4 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 0.378
Genes affected
AIMP2 (HGNC:20609): (aminoacyl tRNA synthetase complex interacting multifunctional protein 2) The protein encoded by this gene is part of the aminoacyl-tRNA synthetase complex, which contains nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. The encoded protein is one of the non-enzymatic factors and is required for assembly and stability of the complex. [provided by RefSeq, May 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3964228).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIMP2 | NM_006303.4 | c.87C>G | p.Asn29Lys | missense_variant | 1/4 | ENST00000223029.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIMP2 | ENST00000223029.8 | c.87C>G | p.Asn29Lys | missense_variant | 1/4 | 1 | NM_006303.4 | P1 | |
AIMP2 | ENST00000395236.2 | c.87C>G | p.Asn29Lys | missense_variant | 1/3 | 2 | |||
AIMP2 | ENST00000400479.6 | c.-251+72C>G | intron_variant | 5 | |||||
AIMP2 | ENST00000415999.1 | c.87C>G | p.Asn29Lys | missense_variant, NMD_transcript_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152160
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000810 AC: 2AN: 247050Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134380
GnomAD3 exomes
AF:
AC:
2
AN:
247050
Hom.:
AF XY:
AC XY:
1
AN XY:
134380
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1458206Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 725400
GnomAD4 exome
AF:
AC:
3
AN:
1458206
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
725400
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
GnomAD4 genome
?
AF:
AC:
2
AN:
152160
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74338
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 | Dec 14, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 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. 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. ClinVar contains an entry for this variant (Variation ID: 986029). This variant has not been reported in the literature in individuals affected with AIMP2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 29 of the AIMP2 protein (p.Asn29Lys). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of methylation at N29 (P = 0.0042);Gain of methylation at N29 (P = 0.0042);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at