14-50247138-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024884.3(L2HGDH):c.1312G>A(p.Ala438Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024884.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
L2HGDH | ENST00000267436.9 | c.1312G>A | p.Ala438Thr | missense_variant | Exon 10 of 10 | 1 | NM_024884.3 | ENSP00000267436.4 | ||
L2HGDH | ENST00000261699.8 | c.1197-9413G>A | intron_variant | Intron 9 of 9 | 1 | ENSP00000261699.4 | ||||
L2HGDH | ENST00000421284.7 | c.1312G>A | p.Ala438Thr | missense_variant | Exon 10 of 11 | 2 | ENSP00000405559.3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251294Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135826
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461812Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727214
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
L-2-hydroxyglutaric aciduria Uncertain:1
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. This variant is present in population databases (rs777120544, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 438 of the L2HGDH protein (p.Ala438Thr). 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