Variant chr19-46660940-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145056.3(DACT3):c.125A>G(p.Gln42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,012 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: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

DACT3
NM_145056.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650

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:

DACT3-AS1 (HGNC:44120): (DACT3 antisense RNA 1)

DACT3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06044981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACT3	NM_145056.3 link	c.125A>G	p.Gln42Arg	missense_variant	1/4	ENST00000391916.7	NP_659493.2	Q96B18
DACT3-AS1	NR_040042.1 link	n.45+532T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DACT3	ENST00000391916.7 link	c.125A>G	p.Gln42Arg	missense_variant	1/4	5	NM_145056.3	ENSP00000375783.2	Q96B18
DACT3	ENST00000410105.2 link	c.125A>G	p.Gln42Arg	missense_variant	1/3	2		ENSP00000387300.1	G5E9H6
DACT3-AS1	ENST00000525008.5 link	n.45+532T>C		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388012

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684960

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:

9.28e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 29, 2024

The c.125A>G (p.Q42R) alteration is located in exon 1 (coding exon 1) of the DACT3 gene. This alteration results from a A to G substitution at nucleotide position 125, causing the glutamine (Q) at amino acid position 42 to be replaced by an arginine (R). 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

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.53

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.23

N;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.35

N;N

REVEL

Benign

0.045

Sift

Benign

0.44

T;T

Sift4G

Benign

0.55

T;D

Polyphen

0.0010

B;B

Vest4

0.23

MutPred

0.34

Gain of MoRF binding (P = 0.0308);Gain of MoRF binding (P = 0.0308);

MVP

0.12

ClinPred

0.072

GERP RS

-0.074

Varity_R

0.092

gMVP

0.27

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