rs113736090
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000170.3(GLDC):c.2919C>T(p.Leu973=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,548,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L973L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000170.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDC | NM_000170.3 | c.2919C>T | p.Leu973= | splice_region_variant, synonymous_variant | 24/25 | ENST00000321612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDC | ENST00000321612.8 | c.2919C>T | p.Leu973= | splice_region_variant, synonymous_variant | 24/25 | 1 | NM_000170.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250538Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135358
GnomAD4 exome AF: 0.0000330 AC: 46AN: 1395758Hom.: 0 Cov.: 25 AF XY: 0.0000215 AC XY: 15AN XY: 698076
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74466
ClinVar
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 11, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2022 | This sequence change affects codon 973 of the GLDC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GLDC protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs113736090, gnomAD 0.01%). This variant has been observed in individual(s) with autism (PMID: 31785789). This variant is also known as 9:6534708. ClinVar contains an entry for this variant (Variation ID: 367174). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | GLDC: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at