9-6610238-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000170.3(GLDC):c.589C>G(p.Leu197Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,718 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 (★). Synonymous variant affecting the same amino acid position (i.e. L197L) has been classified as Likely benign.
Frequency
Consequence
NM_000170.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.589C>G | p.Leu197Val | missense_variant | 4/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.589C>G | p.Leu197Val | missense_variant | 4/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461520Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727014
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2017 | In summary, this variant has uncertain impact on GLDC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function 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 with a GLDC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 197 of the GLDC protein (p.Leu197Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at