14-50628124-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 7P and 1B. PM1PM2PM5PP2BP4
The NM_015915.5(ATL1):c.1213G>A(p.Val405Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V405G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_015915.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATL1 | NM_015915.5 | c.1213G>A | p.Val405Met | missense_variant | 12/14 | ENST00000358385.12 | |
ATL1 | NM_001127713.1 | c.1213G>A | p.Val405Met | missense_variant | 13/14 | ||
ATL1 | NM_181598.4 | c.1213G>A | p.Val405Met | missense_variant | 12/13 | ||
ATL1 | XM_047431430.1 | c.1213G>A | p.Val405Met | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATL1 | ENST00000358385.12 | c.1213G>A | p.Val405Met | missense_variant | 12/14 | 1 | NM_015915.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251308Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135810
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727248
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74474
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 3A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 20, 2023 | This variant is present in population databases (rs201240362, gnomAD 0.008%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 471245). This missense change has been observed in individual(s) with autosomal dominant hereditary spastic paraplegia (PMID: 31594988). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 405 of the ATL1 protein (p.Val405Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at