rs201832111
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001182.5(ALDH7A1):c.682G>A(p.Val228Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,436 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. V228A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001182.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH7A1 | NM_001182.5 | c.682G>A | p.Val228Met | missense_variant | 7/18 | ENST00000409134.8 | |
ALDH7A1 | NM_001201377.2 | c.598G>A | p.Val200Met | missense_variant | 7/18 | ||
ALDH7A1 | NM_001202404.2 | c.682G>A | p.Val228Met | missense_variant | 7/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH7A1 | ENST00000409134.8 | c.682G>A | p.Val228Met | missense_variant | 7/18 | 1 | NM_001182.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250728Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135482
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461132Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726830
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
ClinVar
Submissions by phenotype
Pyridoxine-dependent epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2016 | This sequence change replaces valine with methionine at codon 228 of the ALDH7A1 protein (p.Val228Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs201832111, ExAC 0.01%) but has not been reported in the literature in individuals with a ALDH7A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at