Genetic Variant FCN3:p.Gly17Gly (chr1-27374768-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003665.4(FCN3):c.51G>A(p.Gly17Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,236,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

FCN3
NM_003665.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.91

Publications

1 publications found

Variant links:

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

FCN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP7

Synonymous conserved (PhyloP=-2.91 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN3	NM_003665.4 link	c.51G>A	p.Gly17Gly	synonymous_variant	Exon 1 of 8	ENST00000270879.9	NP_003656.2
FCN3	NM_173452.3 link	c.51G>A	p.Gly17Gly	synonymous_variant	Exon 1 of 7		NP_775628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FCN3	ENST00000270879.9 link	c.51G>A	p.Gly17Gly	synonymous_variant	Exon 1 of 8	1	NM_003665.4	ENSP00000270879.4
FCN3	ENST00000354982.2 link	c.51G>A	p.Gly17Gly	synonymous_variant	Exon 1 of 7	1		ENSP00000347077.2
FCN3	ENST00000481748.1 link	n.38G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
FCN3	ENST00000699963.1 link	c.51G>A	p.Gly17Gly	synonymous_variant	Exon 1 of 7			ENSP00000514719.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

127360

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000324

AC:

AN:

1236246

Hom.:

Cov.:

AF XY:

0.00000501

AC XY:

AN XY:

599156

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26112

American (AMR)

AF:

0.00

AC:

AN:

20314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16726

East Asian (EAS)

AF:

0.00

AC:

AN:

32006

South Asian (SAS)

AF:

0.0000678

AC:

AN:

44248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

997734

Other (OTH)

AF:

0.0000201

AC:

AN:

49632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.1

(source)

DANN

Benign

0.47

PhyloP100

-2.9

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over