19-54885514-T-A

Variant names:

• chr19-54885514-T-A
• NM_002000.4:c.350T>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002000.4. 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
	FCAR	NM_002000.4	MANE Select	c.350T>A	p.Leu117Gln	missense	Exon 3 of 5	NP_001991.1	P24071-1
	FCAR	NM_133272.4		c.314T>A	p.Leu105Gln	missense	Exon 2 of 4	NP_579806.1	P24071-10
	FCAR	NM_133269.4		c.350T>A	p.Leu117Gln	missense	Exon 3 of 5	NP_579803.1	P24071-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	ENST00000355524.8	TSL:1 MANE Select	c.350T>A	p.Leu117Gln	missense	Exon 3 of 5	ENSP00000347714.3	P24071-1
	FCAR	ENST00000359272.8	TSL:1	c.314T>A	p.Leu105Gln	missense	Exon 2 of 4	ENSP00000352218.4	P24071-10
	FCAR	ENST00000391725.7	TSL:1	c.350T>A	p.Leu117Gln	missense	Exon 3 of 5	ENSP00000375605.3	P24071-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		1.3
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.69		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
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

hg19: chr19-55396926;