10-12069104-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_018706.7(DHTKD1):c.71A>G(p.Tyr24Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
DHTKD1
NM_018706.7 missense
NM_018706.7 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 2.85
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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHTKD1 | NM_018706.7 | c.71A>G | p.Tyr24Cys | missense_variant | 1/17 | ENST00000263035.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHTKD1 | ENST00000263035.9 | c.71A>G | p.Tyr24Cys | missense_variant | 1/17 | 1 | NM_018706.7 | P1 | |
DHTKD1 | ENST00000437298.1 | c.71A>G | p.Tyr24Cys | missense_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152118Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459300Hom.: 0 Cov.: 36 AF XY: 0.00000276 AC XY: 2AN XY: 725904
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
2-aminoadipic 2-oxoadipic aciduria Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 08, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 1029713). 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 replaces tyrosine with cysteine at codon 24 of the DHTKD1 protein (p.Tyr24Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Jul 12, 2022 | PM2, PP3 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of phosphorylation at Y24 (P = 0.0605);Loss of phosphorylation at Y24 (P = 0.0605);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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