rs796052269
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_001182.5(ALDH7A1):c.31_33delinsGAG(p.His11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. H11Q) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH7A1 | NM_001182.5 | c.31_33delinsGAG | p.His11Glu | missense_variant | 1/18 | ENST00000409134.8 | |
ALDH7A1 | NM_001202404.2 | c.31_33delinsGAG | p.His11Glu | missense_variant | 1/16 | ||
ALDH7A1 | NM_001201377.2 | c.-54_-52delinsGAG | 5_prime_UTR_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH7A1 | ENST00000409134.8 | c.31_33delinsGAG | p.His11Glu | missense_variant | 1/18 | 1 | NM_001182.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2015 | c.31_33delCACinsGAG: p.His11Glu (H11E) in exon 1 of the ALDH7A1 gene (NM_001182.4). The normal sequence with the bases that are deleted in braces followed by the inserted bases in brackets is: CTGTGTGTG{CAC}[GAG] GCTG. The c.31_33delCACinsGAG variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.31_33delCACinsGAG variant results in an in-frame deletion of a single Histidine residue and the insertion of a single Glutamic acid residue, denoted p.His11Glu (H11E). The H11E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2018 | The c.31_33delCACinsGAG variant, located in coding exon 1 of the ALDH7A1 gene, results from an in-frame deletion of CAC and insertion of GAG at nucleotide positions 31 to 33. This results in the substitution of the histidine residue for a glutamic acid residue at codon 11, an amino acid with highly similar properties. Based on data from gnomAD, this alteration was deposited as two separate missense substitutions (c.31C>G; c.33C>G) each with an overall frequency of approximately 0.01% (21/184172; 20/183384) total alleles studied. The highest observed frequency for each was approximately 0.07% (19/25066; 18/25014) of Latino alleles. This amino acid position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Pyridoxine-dependent epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at