rs142128800
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The ENST00000261772.13(AARS1):āc.1120A>Gā(p.Ile374Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. I374I) has been classified as Likely benign.
Frequency
Consequence
ENST00000261772.13 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AARS1 | NM_001605.3 | c.1120A>G | p.Ile374Val | missense_variant | 9/21 | ENST00000261772.13 | NP_001596.2 | |
AARS1 | XM_047433666.1 | c.1120A>G | p.Ile374Val | missense_variant | 9/16 | XP_047289622.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AARS1 | ENST00000261772.13 | c.1120A>G | p.Ile374Val | missense_variant | 9/21 | 1 | NM_001605.3 | ENSP00000261772 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251478Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 17, 2023 | 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt AARS protein function. ClinVar contains an entry for this variant (Variation ID: 320345). This missense change has been observed in individual(s) with clinical features of AARS-related features (Invitae). This variant is present in population databases (rs142128800, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 374 of the AARS protein (p.Ile374Val). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | AARS1: PM2 - |
Charcot-Marie-Tooth disease axonal type 2N Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at