19-54885501-G-T

Variant names:

• chr19-54885501-G-T
• NM_002000.4:c.337G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002000.4(FCAR):​c.337G>T​(p.Asp113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D113N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FCAR NM_002000.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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

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=0.42166358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAR	NM_002000.4	c.337G>T	p.Asp113Tyr	missense_variant	Exon 3 of 5	ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.337G>T	p.Asp113Tyr	missense_variant	Exon 3 of 5	1	NM_002000.4	ENSP00000347714.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460312 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;.;T;.;.;.;.;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.030	N
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.42	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	.;M;M;M;M;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.8	D;.;D;D;D;D;D;D
REVEL	Benign	0.036
Sift	Uncertain	0.0030	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		1.0, 1.0, 1.0	.;D;D;.;D;.;.;.
Vest4		0.42
MutPred		0.60		.;Gain of methylation at R108 (P = 0.0602);Gain of methylation at R108 (P = 0.0602);Gain of methylation at R108 (P = 0.0602);Gain of methylation at R108 (P = 0.0602);.;.;.;
MVP		0.39
MPC		0.25
ClinPred		0.85	D
GERP RS		-0.13
Varity_R		0.26
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr19-55396913;