NM_000569.8:c.316A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000569.8(FCGR3A):c.316A>G(p.Ile106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 0 hom., cov: 38)

Exomes 𝑓: 0.24 ( 18 hom. )

Failed GnomAD Quality Control

Consequence

FCGR3A
NM_000569.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -6.54

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]

FCGR3A links:

ENSG00000289768 (HGNC:):

ENSG00000289768 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019700825).

BP6

Variant 1-161548424-T-C is Benign according to our data. Variant chr1-161548424-T-C is described in ClinVar as [Benign]. Clinvar id is 156331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3A	NM_000569.8 link	c.316A>G	p.Ile106Val	missense_variant	Exon 3 of 5	ENST00000443193.6	NP_000560.7	P08637

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3A	ENST00000443193.6 link	c.316A>G	p.Ile106Val	missense_variant	Exon 3 of 5	1	NM_000569.8	ENSP00000392047.2		P08637
ENSG00000289768	ENST00000699402.1 link	c.313A>G	p.Ile105Val	missense_variant	Exon 3 of 4			ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

34813

AN:

138490

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.259

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.244

AC:

294808

AN:

1207530

Hom.:

Cov.:

AF XY:

0.245

AC XY:

147694

AN XY:

602250

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.387

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.252

AC:

34860

AN:

138606

Hom.:

Cov.:

AF XY:

0.256

AC XY:

17337

AN XY:

67730

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.435

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.266

Hom.:

ExAC

AF:

0.298

AC:

36139

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0010

DANN

Benign

0.30

DEOGEN2

Benign

0.026

.;T;T;T;.;.;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.034

T;.;.;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.46

.;N;N;N;.;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.22

.;.;N;N;.;.;N

REVEL

Benign

0.026

Sift

Benign

0.54

.;.;T;T;.;.;T

Sift4G

Benign

0.20

.;T;T;T;.;.;.

Polyphen

0.0

.;B;B;B;.;.;.

Vest4

0.024

MPC

0.11

ClinPred

0.0079

GERP RS

-8.9

Varity_R

0.075

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over