19-54885514-T-A

Position:

• chr19-54885514-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002000.4(FCAR):​c.350T>A​(p.Leu117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCAR NM_002000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

Genes affected

FCAR (HGNC:3608): (Fc alpha receptor) This gene is a member of the immunoglobulin gene superfamily and encodes a receptor for the Fc region of IgA. The receptor is a transmembrane glycoprotein present on the surface of myeloid lineage cells such as neutrophils, monocytes, macrophages, and eosinophils, where it mediates immunologic responses to pathogens. It interacts with IgA-opsonized targets and triggers several immunologic defense processes, including phagocytosis, antibody-dependent cell-mediated cytotoxicity, and stimulation of the release of inflammatory mediators. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

FCAR (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCAR	NM_002000.4	c.350T>A	p.Leu117Gln	missense_variant	3/5	ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.350T>A	p.Leu117Gln	missense_variant	3/5	1	NM_002000.4	ENSP00000347714.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2022

The c.350T>A (p.L117Q) alteration is located in exon 3 (coding exon 3) of the FCAR gene. This alteration results from a T to A substitution at nucleotide position 350, causing the leucine (L) at amino acid position 117 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;T;.;.;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.0060	T
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.7	.;H;H;H;H;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.3	D;.;D;D;D;D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;.;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;D;.;.;.
Vest4		0.85
MutPred		0.69		.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;.;.;
MVP		0.53
MPC		0.37
ClinPred		0.97	D
GERP RS		2.2
Varity_R		0.98
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55396926;