rs1360404453

Variant names:

• chr19-46660910-A-C
• NM_145056.3:c.155T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-46660910-A-C
• chr19-46660910-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145056.3(DACT3):​c.155T>G​(p.Met52Arg) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DACT3 NM_145056.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.944

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

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=0.11612418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACT3	NM_145056.3	c.155T>G	p.Met52Arg	missense_variant	Exon 1 of 4	ENST00000391916.7	NP_659493.2
DACT3-AS1	NR_040042.1	n.45+502A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACT3	ENST00000391916.7	c.155T>G	p.Met52Arg	missense_variant	Exon 1 of 4	5	NM_145056.3	ENSP00000375783.2
DACT3	ENST00000410105.2	c.155T>G	p.Met52Arg	missense_variant	Exon 1 of 3	2		ENSP00000387300.1
DACT3-AS1	ENST00000525008.5	n.45+502A>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 149818 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000960

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000667 AC: 1 AN: 149934 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73232

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000960

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0057	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.48	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.076
Sift	Benign	0.19	T;T
Sift4G	Benign	0.36	T;D
Polyphen		0.95	P;B
Vest4		0.31
MutPred		0.25		Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);
MVP		0.22
ClinPred		0.40	T
GERP RS		1.9
Varity_R		0.16
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-47164167;