chr10-12069133-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP7
The NM_018706.7(DHTKD1):c.100C>A(p.Arg34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R34R) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DHTKD1
NM_018706.7 synonymous
NM_018706.7 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.0780
Genes affected
DHTKD1 (HGNC:23537): (dehydrogenase E1 and transketolase domain containing 1) This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP7
Synonymous conserved (PhyloP=0.078 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHTKD1 | NM_018706.7 | c.100C>A | p.Arg34= | synonymous_variant | 1/17 | ENST00000263035.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHTKD1 | ENST00000263035.9 | c.100C>A | p.Arg34= | synonymous_variant | 1/17 | 1 | NM_018706.7 | P1 | |
DHTKD1 | ENST00000437298.1 | c.100C>A | p.Arg34= | synonymous_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1441538Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 715874
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1441538
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Cov.:
36
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0
AN XY:
715874
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
2-aminoadipic 2-oxoadipic aciduria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2021 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 34 of the DHTKD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DHTKD1 protein. 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. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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
Publications
No publications associated with this variant yet.