chr9-6606627-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000170.3(GLDC):c.678C>A(p.His226Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,464 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. H226H) 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 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.678C>A | p.His226Gln | missense_variant | 5/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.678C>A | p.His226Gln | missense_variant | 5/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457464Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725444
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 226 of the GLDC protein (p.His226Gln). This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with GLDC-related conditions. 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 expected to disrupt GLDC 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at