Variant 19-46648943-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145056.3(DACT3):c.1429C>T(p.Arg477Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000597 in 1,339,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

DACT3
NM_145056.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.280

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]

DACT3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2928629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACT3	NM_145056.3 linkuse as main transcript	c.1429C>T	p.Arg477Cys	missense_variant	4/4	ENST00000391916.7	NP_659493.2	Q96B18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACT3	ENST00000391916.7 linkuse as main transcript	c.1429C>T	p.Arg477Cys	missense_variant	4/4	5	NM_145056.3	ENSP00000375783.2		Q96B18
DACT3	ENST00000300875.4 linkuse as main transcript	c.754C>T	p.Arg252Cys	missense_variant	4/4	1		ENSP00000300875.4		A0A0C4DFP1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000505

AC:

AN:

1187230

Hom.:

Cov.:

AF XY:

0.00000347

AC XY:

AN XY:

576174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000407

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.1429C>T (p.R477C) alteration is located in exon 4 (coding exon 4) of the DACT3 gene. This alteration results from a C to T substitution at nucleotide position 1429, causing the arginine (R) at amino acid position 477 to be replaced by a cysteine (C). 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

0.41

BayesDel_addAF

Benign

-0.0068

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.72

T;T

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.34

.;N

PrimateAI

Pathogenic

0.96

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.062

T;T

Polyphen

0.034

.;B

Vest4

0.40

MutPred

0.27

.;Loss of phosphorylation at S478 (P = 0.113);

MVP

0.31

ClinPred

0.89

GERP RS

2.6

Varity_R

0.39

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over