rs1060218
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000159.4(GCDH):c.1173G>T(p.Gly391Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,612,912 control chromosomes in the GnomAD database, including 103,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.31 ( 7709 hom., cov: 30)
Exomes 𝑓: 0.36 ( 95825 hom. )
Consequence
GCDH
NM_000159.4 synonymous
NM_000159.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.11
Genes affected
GCDH (HGNC:4189): (glutaryl-CoA dehydrogenase) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The enzyme exists in the mitochondrial matrix as a homotetramer of 45-kD subunits. Mutations in this gene result in the metabolic disorder glutaric aciduria type 1, which is also known as glutaric acidemia type I. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 12. [provided by RefSeq, Mar 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 19-12897793-G-T is Benign according to our data. Variant chr19-12897793-G-T is described in ClinVar as [Benign]. Clinvar id is 92529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-12897793-G-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.11 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GCDH | NM_000159.4 | c.1173G>T | p.Gly391Gly | synonymous_variant | Exon 11 of 12 | ENST00000222214.10 | NP_000150.1 | |
GCDH | NM_013976.5 | c.1173G>T | p.Gly391Gly | synonymous_variant | Exon 11 of 12 | NP_039663.1 | ||
GCDH | NR_102316.1 | n.1336G>T | non_coding_transcript_exon_variant | Exon 11 of 12 | ||||
GCDH | NR_102317.1 | n.1554G>T | non_coding_transcript_exon_variant | Exon 10 of 11 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.307 AC: 46581AN: 151716Hom.: 7691 Cov.: 30
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GnomAD3 exomes AF: 0.330 AC: 83034AN: 251404Hom.: 14792 AF XY: 0.328 AC XY: 44535AN XY: 135900
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GnomAD4 exome AF: 0.355 AC: 519119AN: 1461078Hom.: 95825 Cov.: 35 AF XY: 0.352 AC XY: 255790AN XY: 726844
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GnomAD4 genome AF: 0.307 AC: 46632AN: 151834Hom.: 7709 Cov.: 30 AF XY: 0.303 AC XY: 22507AN XY: 74198
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glutaric aciduria, type 1 Benign:4
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Nov 19, 2019
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Jun 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:3
Aug 13, 2018
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
not provided Benign:3
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
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Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Feb 16, 2016
Mayo Clinic Laboratories, Mayo Clinic
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Elevated circulating glutaric acid concentration Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at