rs3750940

Positions:

• chr11-12001351-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018057.2(DKK3):​c.351+949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,168 control chromosomes in the GnomAD database, including 3,051 homozygotes. 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 0.19 (3051 hom., cov: 33)
• Consequence: DKK3 NM_001018057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327

Genes affected

DKK3 (HGNC:2893): (dickkopf WNT signaling pathway inhibitor 3) This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

DKK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKK3	NM_001018057.2	c.351+949T>C		intron_variant		ENST00000683431.1	NP_001018067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKK3	ENST00000683431.1	c.351+949T>C		intron_variant			NM_001018057.2	ENSP00000506835.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29504 AN: 152044 Hom.: 3038 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29543 AN: 152168 Hom.: 3051 Cov.: 33 AF XY: 0.195 AC XY: 14523 AN XY: 74420

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.193

Alfa AF: 0.193 Hom.: 4102

Bravo AF: 0.204

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.76

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: rs3750940; hg19: chr11-12022898;