17-45024552-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001288655.2(DCAKD):​c.577C>T​(p.His193Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCAKD
NM_001288655.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1394771).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DCAKDNM_001288655.2 linkuse as main transcriptc.577C>T p.His193Tyr missense_variant 5/5 ENST00000651974.1 NP_001275584.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DCAKDENST00000651974.1 linkuse as main transcriptc.577C>T p.His193Tyr missense_variant 5/5 NM_001288655.2 ENSP00000498268 P1Q8WVC6-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250852
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsMay 13, 2024The c.577C>T (p.H193Y) alteration is located in exon 5 (coding exon 4) of the DCAKD gene. This alteration results from a C to T substitution at nucleotide position 577, causing the histidine (H) at amino acid position 193 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Benign
0.58
DEOGEN2
Benign
0.016
T;T;T;T;T;.
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.26
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.70
.;.;.;T;.;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.14
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;L;L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
0.060
N;N;.;.;.;.
REVEL
Benign
0.18
Sift
Benign
1.0
T;T;.;.;.;.
Sift4G
Benign
1.0
T;T;T;T;T;T
Polyphen
0.0
B;B;B;B;B;.
Vest4
0.30
MutPred
0.55
Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);
MVP
0.31
MPC
0.29
ClinPred
0.034
T
GERP RS
2.8
Varity_R
0.045

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1368844061; hg19: chr17-43101920; API