chr11-11964597-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001018057.2(DKK3):c.920A>G(p.Glu307Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,614,160 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.019 ( 69 hom., cov: 33)
Exomes 𝑓: 0.0063 ( 106 hom. )
Consequence
DKK3
NM_001018057.2 missense
NM_001018057.2 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 2.29
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0050218403).
BP6
?
Variant 11-11964597-T-C is Benign according to our data. Variant chr11-11964597-T-C is described in ClinVar as [Benign]. Clinvar id is 768428.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DKK3 | NM_001018057.2 | c.920A>G | p.Glu307Gly | missense_variant | 7/7 | ENST00000683431.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DKK3 | ENST00000683431.1 | c.920A>G | p.Glu307Gly | missense_variant | 7/7 | NM_001018057.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0187 AC: 2845AN: 152160Hom.: 68 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
2845
AN:
152160
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00845 AC: 2126AN: 251454Hom.: 30 AF XY: 0.00816 AC XY: 1109AN XY: 135908
GnomAD3 exomes
AF:
AC:
2126
AN:
251454
Hom.:
AF XY:
AC XY:
1109
AN XY:
135908
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00625 AC: 9139AN: 1461882Hom.: 106 Cov.: 36 AF XY: 0.00640 AC XY: 4653AN XY: 727240
GnomAD4 exome
AF:
AC:
9139
AN:
1461882
Hom.:
Cov.:
36
AF XY:
AC XY:
4653
AN XY:
727240
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0187 AC: 2854AN: 152278Hom.: 69 Cov.: 33 AF XY: 0.0184 AC XY: 1367AN XY: 74458
GnomAD4 genome
?
AF:
AC:
2854
AN:
152278
Hom.:
Cov.:
33
AF XY:
AC XY:
1367
AN XY:
74458
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
12
ALSPAC
AF:
AC:
17
ESP6500AA
AF:
AC:
249
ESP6500EA
AF:
AC:
45
ExAC
?
AF:
AC:
1135
Asia WGS
AF:
AC:
28
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at