rs745385277
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_001182.5(ALDH7A1):c.119C>T(p.Ala40Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000498 in 1,605,628 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. A40G) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH7A1 | NM_001182.5 | c.119C>T | p.Ala40Val | missense_variant | 1/18 | ENST00000409134.8 | |
ALDH7A1 | NM_001201377.2 | c.35C>T | p.Ala12Val | missense_variant | 1/18 | ||
ALDH7A1 | NM_001202404.2 | c.119C>T | p.Ala40Val | missense_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH7A1 | ENST00000409134.8 | c.119C>T | p.Ala40Val | missense_variant | 1/18 | 1 | NM_001182.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000128 AC: 3AN: 234596Hom.: 0 AF XY: 0.00000788 AC XY: 1AN XY: 126874
GnomAD4 exome AF: 0.00000482 AC: 7AN: 1453456Hom.: 0 Cov.: 32 AF XY: 0.00000692 AC XY: 5AN XY: 722178
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
Pyridoxine-dependent epilepsy Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 40 of the ALDH7A1 protein (p.Ala40Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ALDH7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 350587). 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 ALDH7A1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at