rs747736821
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000170.3(GLDC):āc.270G>Cā(p.Leu90Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000819 in 1,611,616 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L90M) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.270G>C | p.Leu90Phe | missense_variant | 2/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.270G>C | p.Leu90Phe | missense_variant | 2/25 | 1 | NM_000170.3 | P1 | |
GLDC | ENST00000639954.1 | n.114G>C | non_coding_transcript_exon_variant | 1/23 | 5 | ||||
GLDC | ENST00000640592.1 | n.153G>C | non_coding_transcript_exon_variant | 1/16 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152196Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251298Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135852
GnomAD4 exome AF: 0.0000850 AC: 124AN: 1459302Hom.: 0 Cov.: 29 AF XY: 0.0000991 AC XY: 72AN XY: 726178
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152314Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74490
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 90 of the GLDC protein (p.Leu90Phe). This variant is present in population databases (rs747736821, gnomAD 0.02%). 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: 531775). 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. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | GLDC: PM2 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.270G>C (p.L90F) alteration is located in exon 2 (coding exon 2) of the GLDC gene. This alteration results from a G to C substitution at nucleotide position 270, causing the leucine (L) at amino acid position 90 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at