dbSNP rs56088921: FCN3:p.Gly17Gly (chr1-27374768-C-A) – 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>T(p.Gly17Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000809 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: 8.1e-7 ( 0 hom. )

Consequence

FCN3
NM_003665.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.91

Publications

0 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=-0.95).

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>T	p.Gly17Gly	synonymous_variant	Exon 1 of 8	ENST00000270879.9	NP_003656.2	O75636-1Q6UY50
FCN3	NM_173452.3 link	c.51G>T	p.Gly17Gly	synonymous_variant	Exon 1 of 7		NP_775628.1	O75636-2Q6UXM4Q6UY50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCN3	ENST00000270879.9 link	c.51G>T	p.Gly17Gly	synonymous_variant	Exon 1 of 8	1	NM_003665.4	ENSP00000270879.4	O75636-1
FCN3	ENST00000354982.2 link	c.51G>T	p.Gly17Gly	synonymous_variant	Exon 1 of 7	1		ENSP00000347077.2	O75636-2
FCN3	ENST00000481748.1 link	n.38G>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
FCN3	ENST00000699963.1 link	c.51G>T	p.Gly17Gly	synonymous_variant	Exon 1 of 7			ENSP00000514719.1	A0A8V8TPG2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.09e-7

AC:

AN:

1236246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

599156

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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:

0.00

AC:

AN:

44248

European-Finnish (FIN)

AF:

0.0000224

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:

0.00

AC:

AN:

49632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.6

(source)

DANN

Benign

0.57

PhyloP100

-2.9

PromoterAI

-0.022

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