9-6589230-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000170.3(GLDC):c.1545G>A(p.Arg515=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,609,682 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R515R) has been classified as Likely benign.
Frequency
Consequence
NM_000170.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.1545G>A | p.Arg515= | synonymous_variant | 12/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.1545G>A | p.Arg515= | synonymous_variant | 12/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0212 AC: 3228AN: 152032Hom.: 54 Cov.: 32
GnomAD3 exomes AF: 0.0227 AC: 5701AN: 251474Hom.: 93 AF XY: 0.0230 AC XY: 3128AN XY: 135912
GnomAD4 exome AF: 0.0265 AC: 38649AN: 1457532Hom.: 606 Cov.: 28 AF XY: 0.0262 AC XY: 18983AN XY: 725458
GnomAD4 genome ? AF: 0.0212 AC: 3228AN: 152150Hom.: 54 Cov.: 32 AF XY: 0.0206 AC XY: 1535AN XY: 74396
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Uncertain significance, no assertion criteria provided | curation | SingHealth Duke-NUS Institute of Precision Medicine | Jun 07, 2017 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 27, 2018 | Variant summary: GLDC c.1545G>A alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.022 in 277184 control chromosomes in the gnomAD database, including 99 homozygotes. The observed variant frequency is approximately 7-fold above the estimated maximal expected allele frequency for a pathogenic variant in GLDC causing Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) phenotype (0.0031), strongly suggesting that the variant is benign. c.1545G>A has been reported in the literature in an individual affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia), though this patient had two pathogenic mutations in trans, supporting a benign impact of the variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 28, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at