17-44004719-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_153006.3(NAGS):āc.56T>Cā(p.Leu19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L19L) has been classified as Benign.
Frequency
Consequence
NM_153006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.41e-7 AC: 1AN: 1348862Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1AN XY: 668810
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hyperammonemia, type III Uncertain:2
The variant c.56T>C (p.Leu19Pro) in the NAGS gene is reported with an estimated allele frequency of 0.0000119 in gnomAD exomes, with no homozygous individuals reported. The nucleotide position is moderately conserved across 35 mammalian species (GERP RS: 2.07). In silico analysis indicates that the variant might be neutral. However, especially in the setting of variable expressivity, it is advised to use in silico prediction tools with caution (PMID:29805046). -
This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 19 of the NAGS protein (p.Leu19Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with NAGS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1297474). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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