1-161544934-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000569.8(FCGR3A):​c.344G>A​(p.Arg115Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FCGR3A
NM_000569.8 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.86
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.052505374).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FCGR3ANM_000569.8 linkuse as main transcriptc.344G>A p.Arg115Gln missense_variant 4/5 ENST00000443193.6 NP_000560.7 P08637

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FCGR3AENST00000443193.6 linkuse as main transcriptc.344G>A p.Arg115Gln missense_variant 4/51 NM_000569.8 ENSP00000392047.2 P08637
ENSG00000289768ENST00000699402.1 linkuse as main transcriptc.341G>A p.Arg114Gln missense_variant 4/4 ENSP00000514363.1 A0A8V8TN80

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249426
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
134938
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1460352
Hom.:
0
Cov.:
34
AF XY:
0.00000964
AC XY:
7
AN XY:
726462
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000189

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 submitterclinical testingAmbry GeneticsMay 30, 2024The c.452G>A (p.R151Q) alteration is located in exon 4 (coding exon 4) of the FCGR3A gene. This alteration results from a G to A substitution at nucleotide position 452, causing the arginine (R) at amino acid position 151 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.14
DANN
Benign
0.70
DEOGEN2
Benign
0.017
.;T;T;T;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0019
N
LIST_S2
Benign
0.35
T;.;.;T;T;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.053
T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.65
.;N;N;N;.;.
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-0.42
.;.;N;N;.;.
REVEL
Benign
0.018
Sift
Benign
0.70
.;.;T;T;.;.
Sift4G
Benign
0.65
.;T;T;T;.;.
Polyphen
0.15
.;B;B;B;.;.
Vest4
0.051
MVP
0.29
MPC
0.15
ClinPred
0.027
T
GERP RS
-4.0
Varity_R
0.068
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1031388823; hg19: chr1-161514724; COSMIC: COSV104676962; COSMIC: COSV104676962; API