rs199767457
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 5P and 6B. PM1PM2PP3BP4BP6BS1
The NM_001182.5(ALDH7A1):āc.1016A>Gā(p.His339Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,612,632 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H339Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001182.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH7A1 | NM_001182.5 | c.1016A>G | p.His339Arg | missense_variant | 12/18 | ENST00000409134.8 | |
ALDH7A1 | NM_001201377.2 | c.932A>G | p.His311Arg | missense_variant | 12/18 | ||
ALDH7A1 | NM_001202404.2 | c.1008+3232A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH7A1 | ENST00000409134.8 | c.1016A>G | p.His339Arg | missense_variant | 12/18 | 1 | NM_001182.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000191 AC: 48AN: 251304Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135810
GnomAD4 exome AF: 0.0000959 AC: 140AN: 1460308Hom.: 0 Cov.: 30 AF XY: 0.0000977 AC XY: 71AN XY: 726580
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74478
ClinVar
Submissions by phenotype
Pyridoxine-dependent epilepsy Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2017 | A variant of uncertain significance has been identified in the ALDH7A1 gene. The H339R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H339R variant is observed in 24/8620 (0.3%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the H339R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at