19-41220722-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_021913.5(AXL):c.172C>G(p.Leu58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021913.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXL | ENST00000301178.9 | c.172C>G | p.Leu58Val | missense_variant | Exon 2 of 20 | 1 | NM_021913.5 | ENSP00000301178.3 | ||
AXL | ENST00000359092.7 | c.172C>G | p.Leu58Val | missense_variant | Exon 2 of 19 | 1 | ENSP00000351995.2 | |||
AXL | ENST00000599659.5 | n.186C>G | non_coding_transcript_exon_variant | Exon 2 of 12 | 1 | |||||
AXL | ENST00000594880.1 | n.189C>G | non_coding_transcript_exon_variant | Exon 2 of 4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152150Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000335 AC: 84AN: 250608Hom.: 0 AF XY: 0.000325 AC XY: 44AN XY: 135512
GnomAD4 exome AF: 0.000108 AC: 158AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 74AN XY: 727122
GnomAD4 genome AF: 0.000217 AC: 33AN: 152150Hom.: 0 Cov.: 31 AF XY: 0.000350 AC XY: 26AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 58 of the AXL protein (p.Leu58Val). This variant is present in population databases (rs200868176, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with AXL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1930503). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt AXL protein function with a negative predictive value of 80%. 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