chr1-161549705-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000569.8(FCGR3A):c.32T>A(p.Leu11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,613,766 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00035 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 3 hom. )
Consequence
FCGR3A
NM_000569.8 missense
NM_000569.8 missense
Scores
4
10
Clinical Significance
Conservation
PhyloP100: 3.49
Genes affected
FCGR3A (HGNC:3619): (Fc gamma receptor IIIa) This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. This gene (FCGR3A) is highly similar to another nearby gene (FCGR3B) located on chromosome 1. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, whereas FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. Mutations in this gene are associated with immunodeficiency 20, and have been linked to susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1690771).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCGR3A | NM_000569.8 | c.32T>A | p.Leu11Gln | missense_variant | 1/5 | ENST00000443193.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCGR3A | ENST00000443193.6 | c.32T>A | p.Leu11Gln | missense_variant | 1/5 | 1 | NM_000569.8 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000348 AC: 53AN: 152086Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000263 AC: 66AN: 251040Hom.: 1 AF XY: 0.000206 AC XY: 28AN XY: 135646
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GnomAD4 exome AF: 0.000402 AC: 588AN: 1461680Hom.: 3 Cov.: 33 AF XY: 0.000389 AC XY: 283AN XY: 727130
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GnomAD4 genome ? AF: 0.000348 AC: 53AN: 152086Hom.: 1 Cov.: 32 AF XY: 0.000283 AC XY: 21AN XY: 74276
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 08, 2022 | The c.140T>A (p.L47Q) alteration is located in exon 1 (coding exon 1) of the FCGR3A gene. This alteration results from a T to A substitution at nucleotide position 140, causing the leucine (L) at amino acid position 47 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;.;T;T;T;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
REVEL
Benign
Polyphen
1.0
.;D;D;D;.;.;.
Vest4
0.68, 0.67
MVP
MPC
ClinPred
T
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