rs374254987
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM5BP6_Very_Strong
The NM_001605.3(AARS1):c.1996G>A(p.Val666Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,588,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V666A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001605.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AARS1 | NM_001605.3 | c.1996G>A | p.Val666Ile | missense_variant | 15/21 | ENST00000261772.13 | |
AARS1 | XM_047433666.1 | c.1992+766G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AARS1 | ENST00000261772.13 | c.1996G>A | p.Val666Ile | missense_variant | 15/21 | 1 | NM_001605.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 14AN: 207254Hom.: 0 AF XY: 0.0000718 AC XY: 8AN XY: 111486
GnomAD4 exome AF: 0.0000432 AC: 62AN: 1436584Hom.: 0 Cov.: 32 AF XY: 0.0000379 AC XY: 27AN XY: 712452
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74346
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at