rs199505558
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001099922.3(ALG13):āc.1831C>Gā(p.Leu611Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,209,548 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. L611F) has been classified as Likely benign.
Frequency
Consequence
NM_001099922.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG13 | NM_001099922.3 | c.1831C>G | p.Leu611Val | missense_variant | 16/27 | ENST00000394780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG13 | ENST00000394780.8 | c.1831C>G | p.Leu611Val | missense_variant | 16/27 | 2 | NM_001099922.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111509Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33687
GnomAD3 exomes AF: 0.0000223 AC: 4AN: 179198Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 66950
GnomAD4 exome AF: 0.00000455 AC: 5AN: 1098039Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3AN XY: 363479
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111509Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33687
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2016 | The p.L611V variant (also known as c.1831C>G), located in coding exon 16 of the ALG13 gene, results from a C to G substitution at nucleotide position 1831. The leucine at codon 611 is replaced by valine, 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 5150 samples with coverage at this position. This amino acid position is not 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 variant remains unclear. - |
Developmental and epileptic encephalopathy, 36 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 611 of the ALG13 protein (p.Leu611Val). This variant is present in population databases (rs199505558, gnomAD 0.03%), 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: 389963). 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at