rs781779462
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001201377.2(ALDH7A1):c.-69C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,552,286 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 (★★).
Frequency
Consequence
NM_001201377.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDH7A1 | NM_001182.5 | c.16C>T | p.Arg6Cys | missense_variant | Exon 1 of 18 | ENST00000409134.8 | NP_001173.2 | |
ALDH7A1 | NM_001201377.2 | c.-69C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 18 | NP_001188306.1 | |||
ALDH7A1 | NM_001202404.2 | c.16C>T | p.Arg6Cys | missense_variant | Exon 1 of 16 | NP_001189333.2 | ||
ALDH7A1 | NM_001201377.2 | c.-69C>T | 5_prime_UTR_variant | Exon 1 of 18 | NP_001188306.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000192 AC: 3AN: 156456Hom.: 0 AF XY: 0.0000241 AC XY: 2AN XY: 82852
GnomAD4 exome AF: 0.0000121 AC: 17AN: 1400094Hom.: 0 Cov.: 32 AF XY: 0.0000101 AC XY: 7AN XY: 690684
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Pyridoxine-dependent epilepsy Uncertain:3
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This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 6 of the ALDH7A1 protein (p.Arg6Cys). This variant is present in population databases (rs781779462, gnomAD 0.005%). 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: 565938). 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. 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