rs119476048
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_015915.5(ATL1):c.773A>G(p.His258Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H258L) has been classified as Pathogenic.
Frequency
Consequence
NM_015915.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.773A>G | p.His258Arg | missense_variant | 8/14 | ENST00000358385.12 | |
ATL1 | NM_001127713.1 | c.773A>G | p.His258Arg | missense_variant | 9/14 | ||
ATL1 | NM_181598.4 | c.773A>G | p.His258Arg | missense_variant | 8/13 | ||
ATL1 | XM_047431430.1 | c.773A>G | p.His258Arg | missense_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.773A>G | p.His258Arg | missense_variant | 8/14 | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 3A Pathogenic:2Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2019 | This sequence change replaces histidine with arginine at codon 258 of the ATL1 protein (p.His258Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. For these reasons, this variant has been classified as Pathogenic. This variant has been reported to have conflicting or insufficient data to determine the effect on ATL1 protein function (PMID: 16537571, 25761634). This variant has been observed to segregate with hereditary spastic paraplegia in a family (PMID: 11685207). ClinVar contains an entry for this variant (Variation ID: 4348). This variant is not present in population databases (ExAC no frequency). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2001 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at