rs3750940

Variant names:

• chr11-12001351-A-G
• rs3750940
• NM_001018057.2:c.351+949T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018057.2. 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
	DKK3	NM_001018057.2	MANE Select	c.351+949T>C		intron	N/A	NP_001018067.1	Q9UBP4
	DKK3	NM_001330220.3		c.351+949T>C		intron	N/A	NP_001317149.1	F6SYF8
	DKK3	NM_013253.5		c.351+949T>C		intron	N/A	NP_037385.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK3	ENST00000683431.1	MANE Select	c.351+949T>C		intron	N/A	ENSP00000506835.1	Q9UBP4
	DKK3	ENST00000326932.8	TSL:1	c.351+949T>C		intron	N/A	ENSP00000314910.4	Q9UBP4
	DKK3	ENST00000396505.7	TSL:1	c.351+949T>C		intron	N/A	ENSP00000379762.2	Q9UBP4

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

African (AFR) AF: 0.185 AC: 7689 AN: 41510

American (AMR) AF: 0.302 AC: 4617 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.0961 AC: 498 AN: 5182

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1543 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12682 AN: 67988

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.193 Hom.: 5748

Bravo AF: 0.204

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3750940;

hg19: chr11-12022898;