19-46649210-C-A

Variant summary

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

The NM_145056.3(DACT3):​c.1162G>T​(p.Val388Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000952 in 1,050,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 9.5e-7 ( 0 hom. )

Consequence

DACT3
NM_145056.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.434
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]

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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=0.12294662).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DACT3NM_145056.3 linkc.1162G>T p.Val388Leu 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.1162G>T p.Val388Leu missense_variant Exon 4 of 4 5 NM_145056.3 ENSP00000375783.2 Q96B18
DACT3ENST00000300875.4 linkc.487G>T p.Val163Leu missense_variant Exon 4 of 4 1 ENSP00000300875.4 A0A0C4DFP1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
9.52e-7
AC:
1
AN:
1050718
Hom.:
0
Cov.:
31
AF XY:
0.00000200
AC XY:
1
AN XY:
500032
show subpopulations
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:
0.00000111
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1162G>T (p.V388L) alteration is located in exon 4 (coding exon 4) of the DACT3 gene. This alteration results from a G to T substitution at nucleotide position 1162, causing the valine (V) at amino acid position 388 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.018
T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.54
T;T
M_CAP
Pathogenic
0.63
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.81
.;L
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-0.53
N;N
REVEL
Benign
0.051
Sift
Benign
0.32
T;T
Sift4G
Benign
0.31
T;T
Polyphen
0.093
.;B
Vest4
0.090
MutPred
0.14
.;Loss of sheet (P = 0.1398);
MVP
0.48
ClinPred
0.12
T
GERP RS
2.4
Varity_R
0.090
gMVP
0.30

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: rs1455286760; hg19: chr19-47152467; API