NM_052939.4:c.1735G>A

Variant names:

• chr1-157689873-C-T
• rs759615906
• NM_052939.4:c.1735G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052939.4(FCRL3):​c.1735G>A​(p.Gly579Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FCRL3 NM_052939.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

Genes affected

FCRL3 (HGNC:18506): (Fc receptor like 3) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains immunoreceptor-tyrosine activation motifs and immunoreceptor-tyrosine inhibitory motifs in its cytoplasmic domain and may play a role in regulation of the immune system. Mutations in this gene have been associated with rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL3	NM_052939.4	c.1735G>A	p.Gly579Arg	missense_variant	Exon 10 of 15	ENST00000368184.8	NP_443171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8	c.1735G>A	p.Gly579Arg	missense_variant	Exon 10 of 15	1	NM_052939.4	ENSP00000357167.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.98	D;D
Vest4		0.48
MutPred		0.56		Gain of MoRF binding (P = 0.0089);Gain of MoRF binding (P = 0.0089);
MVP		0.57
MPC		0.027
ClinPred		0.70	D
GERP RS		0.33
Varity_R		0.22
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs759615906; hg19: chr1-157659663; COSMIC: COSV63841490; COSMIC: COSV63841490;