chr19-46648565-C-T

Variant names:

• chr19-46648565-C-T
• rs780186917
• NM_145056.3:c.1807G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145056.3(DACT3):​c.1807G>A​(p.Val603Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V603L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DACT3 NM_145056.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145056.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACT3	NM_145056.3	MANE Select	c.1807G>A	p.Val603Met	missense	Exon 4 of 4	NP_659493.2	Q96B18
	DACT3	NM_001301046.2		c.1132G>A	p.Val378Met	missense	Exon 4 of 4	NP_001287975.1	A0A0C4DFP1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACT3	ENST00000391916.7	TSL:5 MANE Select	c.1807G>A	p.Val603Met	missense	Exon 4 of 4	ENSP00000375783.2	Q96B18
	DACT3	ENST00000300875.4	TSL:1	c.1132G>A	p.Val378Met	missense	Exon 4 of 4	ENSP00000300875.4	A0A0C4DFP1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727088

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111816

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.6
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.49		Loss of methylation at K604 (P = 0.0164)
MVP		0.32
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.42
gMVP		0.93
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs780186917; hg19: chr19-47151822;