9-6606659-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000170.3(GLDC):āc.646A>Gā(p.Arg216Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,596,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R216W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000170.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.646A>G | p.Arg216Gly | missense_variant | 5/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.646A>G | p.Arg216Gly | missense_variant | 5/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251484Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135918
GnomAD4 exome AF: 0.0000159 AC: 23AN: 1444122Hom.: 0 Cov.: 27 AF XY: 0.0000153 AC XY: 11AN XY: 719772
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
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 | Oct 07, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 216 of the GLDC protein (p.Arg216Gly). This variant is present in population databases (rs140411475, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GLDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 462891). 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 not 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at