Genetic Variant DKK3:p.Gly347Glu (chr11-11964477-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001018057.2(DKK3):c.1040G>A(p.Gly347Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DKK3
NM_001018057.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

0 publications found

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]

DKK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12931395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018057.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DKK3	NM_001018057.2	MANE Select	c.1040G>A	p.Gly347Glu	missense	Exon 7 of 7	NP_001018067.1	Q9UBP4
DKK3	NM_001330220.3		c.1082G>A	p.Gly361Glu	missense	Exon 8 of 8	NP_001317149.1	F6SYF8
DKK3	NM_013253.5		c.1040G>A	p.Gly347Glu	missense	Exon 8 of 8	NP_037385.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DKK3	ENST00000683431.1	MANE Select	c.1040G>A	p.Gly347Glu	missense	Exon 7 of 7	ENSP00000506835.1	Q9UBP4
DKK3	ENST00000326932.8	TSL:1	c.1040G>A	p.Gly347Glu	missense	Exon 8 of 8	ENSP00000314910.4	Q9UBP4
DKK3	ENST00000396505.7	TSL:1	c.1040G>A	p.Gly347Glu	missense	Exon 8 of 8	ENSP00000379762.2	Q9UBP4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459786

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726328

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.49

M_CAP

Benign

0.0060

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PhyloP100

1.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.20

REVEL

Benign

0.042

Sift

Uncertain

0.012

Sift4G

Benign

0.081

Polyphen

0.0050

Vest4

0.22

MutPred

0.22

Gain of solvent accessibility (P = 0.024)

MVP

0.48

MPC

0.42

ClinPred

0.51

GERP RS

3.0

Varity_R

0.048

gMVP

0.64

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over