NM_004423.4:c.161+2928A>C

Variant names:

• chr3-184158724-A-C
• rs1969253
• NM_004423.4:c.161+2928A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004423.4(DVL3):​c.161+2928A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,280 control chromosomes in the GnomAD database, including 19,787 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 0.51 (19787 hom., cov: 29)
• Consequence: DVL3 NM_004423.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 27 publications found

Genes affected

DVL3 (HGNC:3087): (dishevelled segment polarity protein 3) This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila dishevelled gene encodes a cytoplasmic phosphoprotein that regulates cell proliferation. [provided by RefSeq, Jul 2008]

DVL3 Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL3	NM_004423.4	MANE Select	c.161+2928A>C		intron	N/A	NP_004414.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL3	ENST00000313143.9	TSL:1 MANE Select	c.161+2928A>C		intron	N/A	ENSP00000316054.3
	DVL3	ENST00000431765.6	TSL:5	c.161+2928A>C		intron	N/A	ENSP00000405885.1
	DVL3	ENST00000423300.1	TSL:5	n.293+1657A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.509 AC: 76962 AN: 151170 Hom.: 19755 Cov.: 29

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.509 AC: 77042 AN: 151280 Hom.: 19787 Cov.: 29 AF XY: 0.509 AC XY: 37545 AN XY: 73808

African (AFR) AF: 0.526 AC: 21648 AN: 41166

American (AMR) AF: 0.417 AC: 6346 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1644 AN: 3464

East Asian (EAS) AF: 0.551 AC: 2816 AN: 5114

South Asian (SAS) AF: 0.584 AC: 2805 AN: 4804

European-Finnish (FIN) AF: 0.451 AC: 4652 AN: 10310

Middle Eastern (MID) AF: 0.503 AC: 146 AN: 290

European-Non Finnish (NFE) AF: 0.522 AC: 35465 AN: 67892

Other (OTH) AF: 0.500 AC: 1055 AN: 2112

Alfa AF: 0.518 Hom.: 50324

Bravo AF: 0.501

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.10
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

Other links and lift over

dbSNP: rs1969253; hg19: chr3-183876512;