ClinVar Miner

Submissions for variant NM_001099922.3(ALG13):c.756T>G (p.Phe252Leu)

gnomAD frequency: 0.00007  dbSNP: rs915629293
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000696177 SCV000824726 uncertain significance Developmental and epileptic encephalopathy, 36 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 252 of the ALG13 protein (p.Phe252Leu). This variant is present in population databases (no rsID available, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with ALG13-related conditions. ClinVar contains an entry for this variant (Variation ID: 574279). 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 ALG13 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.
Ambry Genetics RCV002315995 SCV000848125 uncertain significance Inborn genetic diseases 2016-11-01 criteria provided, single submitter clinical testing The p.F252L variant (also known as c.756T>G), located in coding exon 5 of the ALG13 gene, results from a T to G substitution at nucleotide position 756. The phenylalanine at codon 252 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5147 samples with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001592887 SCV001816522 likely benign not provided 2021-04-28 criteria provided, single submitter clinical testing

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