rs58528748
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001182.5(ALDH7A1):c.203C>A(p.Thr68Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,613,406 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).
Frequency
Consequence
NM_001182.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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ALDH7A1 | NM_001182.5 | c.203C>A | p.Thr68Asn | missense_variant | Exon 2 of 18 | ENST00000409134.8 | NP_001173.2 | |
ALDH7A1 | NM_001201377.2 | c.119C>A | p.Thr40Asn | missense_variant | Exon 2 of 18 | NP_001188306.1 | ||
ALDH7A1 | NM_001202404.2 | c.203C>A | p.Thr68Asn | missense_variant | Exon 2 of 16 | NP_001189333.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000310 AC: 47AN: 151606Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251374Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135880
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461684Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26AN XY: 727148
GnomAD4 genome AF: 0.000310 AC: 47AN: 151722Hom.: 0 Cov.: 32 AF XY: 0.000310 AC XY: 23AN XY: 74102
ClinVar
Submissions by phenotype
Pyridoxine-dependent epilepsy Uncertain:3Benign:1
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This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Inborn genetic diseases Uncertain:1
The c.203C>A (p.T68N) alteration is located in exon 2 (coding exon 2) of the ALDH7A1 gene. This alteration results from a C to A substitution at nucleotide position 203, causing the threonine (T) at amino acid position 68 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Intractable seizure Uncertain:1
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not provided Uncertain:1
Published functional studies using an E.coli-based expression system suggest that this variant results in decreased expression; however additional studies are needed to validate the functional effect of this variant in vivo (Coughlin et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30043187) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at