rs751861796
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS1_Supporting
The NM_015915.5(ATL1):c.1556G>A(p.Ser519Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000326 in 1,594,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015915.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.1556G>A | p.Ser519Asn | missense_variant | Exon 13 of 14 | ENST00000358385.12 | NP_056999.2 | |
ATL1 | XM_047431430.1 | c.1556G>A | p.Ser519Asn | missense_variant | Exon 14 of 15 | XP_047287386.1 | ||
ATL1 | NM_001127713.1 | c.1551+1537G>A | intron_variant | Intron 13 of 13 | NP_001121185.1 | |||
ATL1 | NM_181598.4 | c.1551+1537G>A | intron_variant | Intron 12 of 12 | NP_853629.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152106Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000206 AC: 5AN: 242362Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131084
GnomAD4 exome AF: 0.0000298 AC: 43AN: 1442588Hom.: 0 Cov.: 27 AF XY: 0.0000251 AC XY: 18AN XY: 718042
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74298
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 3A Uncertain:2
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 519 of the ATL1 protein (p.Ser519Asn). This variant is present in population databases (rs751861796, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of ATL1-related conditions (PMID: 15596607; Invitae). ClinVar contains an entry for this variant (Variation ID: 538582). 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 not expected to disrupt ATL1 protein function with a negative predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ATL1 function (PMID: 17321752). 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. -
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Hereditary spastic paraplegia 3A;C3150972:Neuropathy, hereditary sensory, type 1D Other:1
Variant interpreted as Uncertain significance and reported on 03-07-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at