9-134912570-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002003.5(FCN1):c.514T>C(p.Trp172Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
FCN1
NM_002003.5 missense
NM_002003.5 missense
Scores
5
6
3
Clinical Significance
Conservation
PhyloP100: 7.33
Genes affected
FCN1 (HGNC:3623): (ficolin 1) The ficolin family of proteins are characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.862
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCN1 | NM_002003.5 | c.514T>C | p.Trp172Arg | missense_variant | 7/9 | ENST00000371806.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCN1 | ENST00000371806.4 | c.514T>C | p.Trp172Arg | missense_variant | 7/9 | 1 | NM_002003.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251358Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135874
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461816Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9AN XY: 727218
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74476
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2023 | The c.514T>C (p.W172R) alteration is located in exon 7 (coding exon 7) of the FCN1 gene. This alteration results from a T to C substitution at nucleotide position 514, causing the tryptophan (W) at amino acid position 172 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
Gain of disorder (P = 0.0267);Gain of disorder (P = 0.0267);
MVP
MPC
0.72
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at