rs1555750471
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000159.4(GCDH):āc.550A>Gā(p.Ser184Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
GCDH
NM_000159.4 missense
NM_000159.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 4.56
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
In a strand (size 2) in uniprot entity GCDH_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_000159.4
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GCDH | NM_000159.4 | c.550A>G | p.Ser184Gly | missense_variant | 7/12 | ENST00000222214.10 | NP_000150.1 | |
GCDH | NM_013976.5 | c.550A>G | p.Ser184Gly | missense_variant | 7/12 | NP_039663.1 | ||
GCDH | NR_102316.1 | n.713A>G | non_coding_transcript_exon_variant | 7/12 | ||||
GCDH | NR_102317.1 | n.966A>G | non_coding_transcript_exon_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GCDH | ENST00000222214.10 | c.550A>G | p.Ser184Gly | missense_variant | 7/12 | 1 | NM_000159.4 | ENSP00000222214.4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461818Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727212
GnomAD4 exome
AF:
AC:
3
AN:
1461818
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727212
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Glutaric aciduria, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | TIDEX, University of British Columbia | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
D;.
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of glycosylation at S184 (P = 0.0121);Loss of glycosylation at S184 (P = 0.0121);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at