rs532781899

Variant names:

• chr1-27373179-AGG-A
• rs532781899
• NM_003665.4:c.348_349delCC

Your query was ambiguous. Multiple possible variants found:

• chr1-27373179-AGG-A
• chr1-27373179-AGG-AG
• chr1-27373179-AGG-AGGG

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003665.4(FCN3):​c.348_349delCC​(p.Leu117ProfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCN3 NM_003665.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 46 publications found

Genes affected

FCN3 (HGNC:3625): (ficolin 3) Ficolins are a group of proteins which consist of a collagen-like domain and a fibrinogen-like domain. In human serum, there are two types of ficolins, both of which have lectin activity. The protein encoded by this gene is a thermolabile beta-2-macroglycoprotein found in all human serum and is a member of the ficolin/opsonin p35 lectin family. The protein, which was initially identified based on its reactivity with sera from patients with systemic lupus erythematosus, has been shown to have a calcium-independent lectin activity. The protein can activate the complement pathway in association with MASPs and sMAP, thereby aiding in host defense through the activation of the lectin pathway. Alternative splicing occurs at this locus and two variants, each encoding a distinct isoform, have been identified. [provided by RefSeq, Jul 2008]

FCN3 Gene-Disease associations (from GenCC):

• immunodeficiency due to ficolin3 deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003665.4. 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
	FCN3	NM_003665.4	MANE Select	c.348_349delCC	p.Leu117ProfsTer5	frameshift	Exon 5 of 8	NP_003656.2
	FCN3	NM_173452.3		c.315_316delCC	p.Leu106ProfsTer5	frameshift	Exon 4 of 7	NP_775628.1	O75636-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN3	ENST00000270879.9	TSL:1 MANE Select	c.348_349delCC	p.Leu117ProfsTer5	frameshift	Exon 5 of 8	ENSP00000270879.4	O75636-1
	FCN3	ENST00000354982.2	TSL:1	c.315_316delCC	p.Leu106ProfsTer5	frameshift	Exon 4 of 7	ENSP00000347077.2	O75636-2
	FCN3	ENST00000859507.1		c.348_349delCC	p.Leu117ProfsTer5	frameshift	Exon 5 of 9	ENSP00000529566.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs532781899; hg19: chr1-27699670;