Variant 1-161548632-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000569.8(FCGR3A):c.108G>C(p.Arg36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FCGR3A
NM_000569.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.421

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3521728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3A	NM_000569.8 linkuse as main transcript	c.108G>C	p.Arg36Ser	missense_variant	3/5	ENST00000443193.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3A	ENST00000443193.6 linkuse as main transcript	c.108G>C	p.Arg36Ser	missense_variant	3/5	1	NM_000569.8	P4

Frequencies

GnomAD3 genomes

AF:

0.0000793

AC:

AN:

151338

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

249784

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135038

show subpopulations

Gnomad AFR exome

AF:

0.000378

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461056

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000792

AC:

AN:

151456

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.000269

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00144

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.75

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.12

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

M_CAP

Benign

0.0065

MetaRNN

Benign

0.35

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.6e-8

A;A;A;A;A

PrimateAI

Benign

0.28

REVEL

Benign

0.12

Polyphen

0.98

.;D;D;D;.;.;.

Vest4

0.29

MVP

0.26

MPC

0.56

ClinPred

0.41

GERP RS

-2.6

Varity_R

0.77

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over