rs775904247
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001605.3(AARS1):c.510C>A(p.Asn170Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,012 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 (★). Synonymous variant affecting the same amino acid position (i.e. N170N) has been classified as Likely benign.
Frequency
Consequence
NM_001605.3 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 | UniProt |
---|---|---|---|---|---|---|---|
AARS1 | NM_001605.3 | c.510C>A | p.Asn170Lys | missense_variant | 5/21 | ENST00000261772.13 | |
AARS1 | XM_047433666.1 | c.510C>A | p.Asn170Lys | missense_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AARS1 | ENST00000261772.13 | c.510C>A | p.Asn170Lys | missense_variant | 5/21 | 1 | NM_001605.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251320Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135836
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727246
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 24, 2023 | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 170 of the AARS protein (p.Asn170Lys). 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: 239034). This missense change has been observed in individual(s) with AARS-related conditions (PMID: 24627108). This variant is present in population databases (rs775904247, gnomAD 0.002%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at