chr17-45034360-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001288655.2(DCAKD):c.143G>A(p.Arg48His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
DCAKD
NM_001288655.2 missense
NM_001288655.2 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 1.78
Genes affected
DCAKD (HGNC:26238): (dephospho-CoA kinase domain containing) Predicted to enable dephospho-CoA kinase activity. Predicted to be involved in coenzyme A biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
NMT1 (HGNC:7857): (N-myristoyltransferase 1) Myristate, a rare 14-carbon saturated fatty acid, is cotranslationally attached by an amide linkage to the N-terminal glycine residue of cellular and viral proteins with diverse functions. N-myristoyltransferase (NMT; EC 2.3.1.97) catalyzes the transfer of myristate from CoA to proteins. N-myristoylation appears to be irreversible and is required for full expression of the biologic activities of several N-myristoylated proteins, including the alpha subunit of the signal-transducing guanine nucleotide-binding protein (G protein) GO (GNAO1; MIM 139311) (Duronio et al., 1992 [PubMed 1570339]).[supplied by OMIM, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCAKD | NM_001288655.2 | c.143G>A | p.Arg48His | missense_variant | 3/5 | ENST00000651974.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCAKD | ENST00000651974.1 | c.143G>A | p.Arg48His | missense_variant | 3/5 | NM_001288655.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247316Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133910
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461598Hom.: 0 Cov.: 36 AF XY: 0.0000151 AC XY: 11AN XY: 727076
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.143G>A (p.R48H) alteration is located in exon 3 (coding exon 2) of the DCAKD gene. This alteration results from a G to A substitution at nucleotide position 143, causing the arginine (R) at amino acid position 48 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;M;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.;D;.;.
REVEL
Benign
Sift
Uncertain
D;D;.;D;.;.
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;D;D;D;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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