16-70252748-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001605.3(AARS1):āc.2880G>Cā(p.Gln960His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q960P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001605.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AARS1 | NM_001605.3 | c.2880G>C | p.Gln960His | missense_variant | 21/21 | ENST00000261772.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AARS1 | ENST00000261772.13 | c.2880G>C | p.Gln960His | missense_variant | 21/21 | 1 | NM_001605.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251362Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461804Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727218
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.2880G>C (p.Q960H) alteration is located in exon 21 (coding exon 20) of the AARS gene. This alteration results from a G to C substitution at nucleotide position 2880, causing the glutamine (Q) at amino acid position 960 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 03, 2023 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 960 of the AARS protein (p.Gln960His). This variant is present in population databases (rs779509100, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 2234316). 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. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at