chrX-111722833-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001099922.3(ALG13):c.1476G>C(p.Gln492His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,085,254 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q492E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001099922.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG13 | NM_001099922.3 | c.1476G>C | p.Gln492His | missense_variant | 13/27 | ENST00000394780.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG13 | ENST00000394780.8 | c.1476G>C | p.Gln492His | missense_variant | 13/27 | 2 | NM_001099922.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 112369Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34529 FAILED QC
GnomAD3 exomes AF: 0.0000241 AC: 4AN: 165848Hom.: 0 AF XY: 0.0000183 AC XY: 1AN XY: 54792
GnomAD4 exome AF: 0.00000276 AC: 3AN: 1085254Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 351774
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 112369Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34529
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 36 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces glutamine with histidine at codon 492 of the ALG13 protein (p.Gln492His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs760560180, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with ALG13-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 28, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at