FCGR3A p.Asp166Asp

Variant names:

• chr1-161544779-T-T
• NM_000569.8:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-161544780--
• chr1-161544780-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000569.8(FCGR3A):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCGR3A NM_000569.8 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

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]

FCGR3A Gene-Disease associations (from GenCC):

• autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000273112 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000569.8. 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
	FCGR3A	NM_000569.8	MANE Select	c.		exon_region	Exon 4 of 5	NP_000560.7
	FCGR3A	NM_001127592.2		c.		exon_region	Exon 4 of 5	NP_001121064.2	P08637
	FCGR3A	NM_001127593.1		c.		exon_region	Exon 5 of 6	NP_001121065.1	P08637

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3A	ENST00000443193.6	TSL:1 MANE Select	c.		exon_region	Exon 4 of 5	ENSP00000392047.2	P08637
	FCGR3A	ENST00000946731.1		c.		exon_region	Exon 5 of 6	ENSP00000616790.1
	FCGR3A	ENST00000699401.1		c.		exon_region	Exon 5 of 6	ENSP00000514362.1	A0A8V8TQ03

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-161514569;