rs1486918303

Variant summary

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

The NM_145056.3(DACT3):​c.1456G>T​(p.Asp486Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D486N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DACT3
NM_145056.3 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43
Variant links:
Genes affected
DACT3 (HGNC:30745): (dishevelled binding antagonist of beta catenin 3) Predicted to enable delta-catenin binding activity; protein kinase A binding activity; and protein kinase C binding activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of cell growth. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.26162827).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DACT3NM_145056.3 linkc.1456G>T p.Asp486Tyr missense_variant Exon 4 of 4 ENST00000391916.7 NP_659493.2 Q96B18

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DACT3ENST00000391916.7 linkc.1456G>T p.Asp486Tyr missense_variant Exon 4 of 4 5 NM_145056.3 ENSP00000375783.2 Q96B18
DACT3ENST00000300875.4 linkc.781G>T p.Asp261Tyr missense_variant Exon 4 of 4 1 ENSP00000300875.4 A0A0C4DFP1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1206412
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
586132
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.040
T;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.59
T;T
M_CAP
Pathogenic
0.50
D
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.34
.;N
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0050
D;D
Sift4G
Benign
0.075
T;D
Polyphen
0.98
.;D
Vest4
0.25
MutPred
0.24
.;Gain of helix (P = 0.0078);
MVP
0.44
ClinPred
0.70
D
GERP RS
2.8
Varity_R
0.22
gMVP
0.35

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: rs1486918303; hg19: chr19-47152173; API