rs776366099
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_015459.5(ATL3):āc.557T>Gā(p.Leu186Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,595,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L186P) has been classified as Uncertain significance.
Frequency
Consequence
NM_015459.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL3 | NM_015459.5 | c.557T>G | p.Leu186Arg | missense_variant | 5/13 | ENST00000398868.8 | |
ATL3 | NM_001290048.2 | c.503T>G | p.Leu168Arg | missense_variant | 5/13 | ||
ATL3 | XM_047426725.1 | c.713T>G | p.Leu238Arg | missense_variant | 6/14 | ||
ATL3 | XM_006718493.2 | c.557T>G | p.Leu186Arg | missense_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL3 | ENST00000398868.8 | c.557T>G | p.Leu186Arg | missense_variant | 5/13 | 1 | NM_015459.5 | ||
ENST00000540307.1 | n.247+1193A>C | intron_variant, non_coding_transcript_variant | 3 | ||||||
ATL3 | ENST00000538786.1 | c.503T>G | p.Leu168Arg | missense_variant | 5/13 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000863 AC: 2AN: 231636Hom.: 0 AF XY: 0.00000793 AC XY: 1AN XY: 126064
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1443004Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 717536
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74376
ClinVar
Submissions by phenotype
Neuropathy, hereditary sensory, type 1F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATL3-related disease. This variant is present in population databases (rs776366099, ExAC 0.002%). This sequence change replaces leucine with arginine at codon 186 of the ATL3 protein (p.Leu186Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at