rs119476049
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PP2PP3_StrongPP5_Very_Strong
The NM_015915.5(ATL1):c.650G>A(p.Arg217Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_015915.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.650G>A | p.Arg217Gln | missense_variant | 7/14 | ENST00000358385.12 | |
ATL1 | NM_001127713.1 | c.650G>A | p.Arg217Gln | missense_variant | 8/14 | ||
ATL1 | NM_181598.4 | c.650G>A | p.Arg217Gln | missense_variant | 7/13 | ||
ATL1 | XM_047431430.1 | c.650G>A | p.Arg217Gln | missense_variant | 8/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.650G>A | p.Arg217Gln | missense_variant | 7/14 | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460844Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726758
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 3A Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2002 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Paris Brain Institute, Inserm - ICM | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 08, 2022 | ClinVar contains an entry for this variant (Variation ID: 4349). This missense change has been observed in individuals with spastic paraplegia (PMID: 12112092). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 217 of the ATL1 protein (p.Arg217Gln). 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 expected to disrupt ATL1 protein function. Experimental studies have shown that this missense change affects ATL1 function (PMID: 16537571, 21368113, 23999326, 25761634). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at