6-18237442-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_003472.4(DEK):​c.837T>A​(p.Ser279Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,610,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

DEK
NM_003472.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62
Variant links:
Genes affected
DEK (HGNC:2768): (DEK proto-oncogene) This gene encodes a protein with one SAP domain. This protein binds to cruciform and superhelical DNA and induces positive supercoils into closed circular DNA, and is also involved in splice site selection during mRNA processing. Chromosomal aberrations involving this region, increased expression of this gene, and the presence of antibodies against this protein are all associated with various diseases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1
In a modified_residue ADP-ribosylserine (size 0) in uniprot entity DEK_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06358746).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEKNM_003472.4 linkc.837T>A p.Ser279Arg missense_variant 8/11 ENST00000652689.1 NP_003463.1 P35659-1
DEKNM_001134709.2 linkc.735T>A p.Ser245Arg missense_variant 7/10 NP_001128181.1 P35659-2
DEKXM_024446544.2 linkc.837T>A p.Ser279Arg missense_variant 8/11 XP_024302312.1
DEKXM_047419335.1 linkc.*75T>A downstream_gene_variant XP_047275291.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEKENST00000652689.1 linkc.837T>A p.Ser279Arg missense_variant 8/11 NM_003472.4 ENSP00000498653.1 P35659-1

Frequencies

GnomAD3 genomes
AF:
0.000212
AC:
32
AN:
151190
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000656
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00145
GnomAD3 exomes
AF:
0.0000442
AC:
11
AN:
248942
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134608
show subpopulations
Gnomad AFR exome
AF:
0.000432
Gnomad AMR exome
AF:
0.000117
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:
0.0000240
AC:
35
AN:
1459008
Hom.:
0
Cov.:
31
AF XY:
0.0000152
AC XY:
11
AN XY:
725838
show subpopulations
Gnomad4 AFR exome
AF:
0.000902
Gnomad4 AMR exome
AF:
0.0000453
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:
0.0000498
GnomAD4 genome
AF:
0.000212
AC:
32
AN:
151190
Hom.:
1
Cov.:
32
AF XY:
0.000271
AC XY:
20
AN XY:
73772
show subpopulations
Gnomad4 AFR
AF:
0.000656
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00145
Alfa
AF:
0.000142
Hom.:
0
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000577
AC:
7

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 02, 2024The c.837T>A (p.S279R) alteration is located in exon 8 (coding exon 7) of the DEK gene. This alteration results from a T to A substitution at nucleotide position 837, causing the serine (S) at amino acid position 279 to be replaced by an arginine (R). 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
Pathogenic
0.59
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.88
D;D;.
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.064
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.70
N;N;N
REVEL
Benign
0.021
Sift
Uncertain
0.021
D;D;T
Sift4G
Benign
0.37
T;T;T
Polyphen
0.090
B;.;.
Vest4
0.24
MutPred
0.29
Loss of phosphorylation at S279 (P = 0.0037);.;.;
MVP
0.75
MPC
0.11
ClinPred
0.039
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.075

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: rs138816210; hg19: chr6-18237673; API