rs370964168
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000170.3(GLDC):c.913C>A(p.Pro305Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,832 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. P305P) 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.913C>A | p.Pro305Thr | missense_variant | 7/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.913C>A | p.Pro305Thr | missense_variant | 7/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251238Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135814
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727222
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces proline with threonine at codon 305 of the GLDC protein (p.Pro305Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs370964168, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with GLDC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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