NM_001018057.2:c.1013C>A

Variant summary

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

The NM_001018057.2(DKK3):​c.1013C>A​(p.Ala338Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

DKK3
NM_001018057.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267
Variant links:
Genes affected
DKK3 (HGNC:2893): (dickkopf WNT signaling pathway inhibitor 3) This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

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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=0.12283167).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DKK3NM_001018057.2 linkc.1013C>A p.Ala338Glu missense_variant Exon 7 of 7 ENST00000683431.1 NP_001018067.1 Q9UBP4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DKK3ENST00000683431.1 linkc.1013C>A p.Ala338Glu missense_variant Exon 7 of 7 NM_001018057.2 ENSP00000506835.1 Q9UBP4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
3.1
DANN
Benign
0.33
DEOGEN2
Benign
0.077
T;T;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.47
.;T;T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.030
N;N;N
REVEL
Benign
0.058
Sift
Benign
0.74
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.96
D;D;D
Vest4
0.26
MutPred
0.23
.;.;Gain of solvent accessibility (P = 0.0145);
MVP
0.43
MPC
0.38
ClinPred
0.12
T
GERP RS
-2.4
Varity_R
0.037
gMVP
0.20

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: rs114429255; hg19: chr11-11986051; API