rs1486918303

Variant names:

• chr19-46648916-C-A
• rs1486918303
• NM_145056.3:c.1456G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-46648916-C-A
• chr19-46648916-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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

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
DACT3	NM_145056.3	c.1456G>T	p.Asp486Tyr	missense_variant	Exon 4 of 4	ENST00000391916.7	NP_659493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACT3	ENST00000391916.7	c.1456G>T	p.Asp486Tyr	missense_variant	Exon 4 of 4	5	NM_145056.3	ENSP00000375783.2
DACT3	ENST00000300875.4	c.781G>T	p.Asp261Tyr	missense_variant	Exon 4 of 4	1		ENSP00000300875.4

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

Other links and lift over

dbSNP: rs1486918303; hg19: chr19-47152173;