NM_003472.4:c.1001C>A

Variant names:

• chr6-18236498-G-T
• rs1790653898
• NM_003472.4:c.1001C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003472.4(DEK):​c.1001C>A​(p.Ala334Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEK NM_003472.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3689774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003472.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEK	NM_003472.4	MANE Select	c.1001C>A	p.Ala334Asp	missense	Exon 9 of 11	NP_003463.1	P35659-1
	DEK	NM_001134709.2		c.899C>A	p.Ala300Asp	missense	Exon 8 of 10	NP_001128181.1	P35659-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEK	ENST00000652689.1	MANE Select	c.1001C>A	p.Ala334Asp	missense	Exon 9 of 11	ENSP00000498653.1	P35659-1
	DEK	ENST00000852490.1		c.1025C>A	p.Ala342Asp	missense	Exon 10 of 12	ENSP00000522549.1
	DEK	ENST00000507591.2	TSL:2	c.1001C>A	p.Ala334Asp	missense	Exon 9 of 10	ENSP00000423427.2	H0Y993

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.92	N
REVEL	Benign	0.22
Sift	Benign	0.55	T
Sift4G	Benign	0.55	T
Polyphen		0.56	P
Vest4		0.39
MutPred		0.60		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.88
MPC		0.18
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs1790653898; hg19: chr6-18236729; COSMIC: COSV55236413; COSMIC: COSV55236413;