Variant 17-45024489-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001288655.2(DCAKD):c.640G>A(p.Ala214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000517 in 1,613,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

DCAKD
NM_001288655.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

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]

DCAKD links:

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]

NMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044440776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAKD	NM_001288655.2 link	c.640G>A	p.Ala214Thr	missense_variant	5/5	ENST00000651974.1	NP_001275584.1	Q8WVC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAKD	ENST00000651974.1 link	c.640G>A	p.Ala214Thr	missense_variant	5/5		NM_001288655.2	ENSP00000498268.1		Q8WVC6-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000307

AC:

AN:

251132

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000388

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000545

AC:

797

AN:

1461100

Hom.:

Cov.:

AF XY:

0.000519

AC XY:

377

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000664

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000243

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000440

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000652

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

Aug 12, 2021

The c.640G>A (p.A214T) alteration is located in exon 5 (coding exon 4) of the DCAKD gene. This alteration results from a G to A substitution at nucleotide position 640, causing the alanine (A) at amino acid position 214 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.031

T;T;T;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.61

.;.;.;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.044

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L;L;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.16

N;N;.;.;.

REVEL

Benign

0.048

Sift

Benign

0.38

T;T;.;.;.

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.11

B;B;B;B;B

Vest4

0.19

MVP

0.35

MPC

0.25

ClinPred

0.034

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over