rs929539458

Variant names:

• chr1-206909520-C-G
• rs929539458
• NM_005449.5:c.986G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-206909520-C-G
• chr1-206909520-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005449.5(FCMR):​c.986G>C​(p.Gly329Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000831 in 1,324,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G329G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: FCMR NM_005449.5 missense, splice_region
• Scores: Splicing: ADA: 0.9978
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.975
• Publications: 0 publications found

Genes affected

FCMR (HGNC:14315): (Fc mu receptor) Fc receptors specifically bind to the Fc region of immunoglobulins (Igs) to mediate the unique functions of each Ig class. FAIM3 encodes an Fc receptor for IgM (see MIM 147020) (Kubagawa et al., 2009 [PubMed 19858324]; Shima et al., 2010 [PubMed 20042454]).[supplied by OMIM, Jul 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.986G>C	p.Gly329Ala	missense_variant, splice_region_variant	Exon 7 of 8	ENST00000367091.8	NP_005440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCMR	ENST00000367091.8	c.986G>C	p.Gly329Ala	missense_variant, splice_region_variant	Exon 7 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 0.00000427 AC: 5 AN: 1172224 Hom.: 0 Cov.: 30 AF XY: 0.00000356 AC XY: 2 AN XY: 562092

African (AFR) AF: 0.000214 AC: 5 AN: 23408

American (AMR) AF: 0.00 AC: 0 AN: 8872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16508

East Asian (EAS) AF: 0.00 AC: 0 AN: 26804

South Asian (SAS) AF: 0.00 AC: 0 AN: 43954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 972734

Other (OTH) AF: 0.00 AC: 0 AN: 48080

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74354

African (AFR) AF: 0.000145 AC: 6 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.986G>C (p.G329A) alteration is located in exon 7 (coding exon 7) of the FCMR gene. This alteration results from a G to C substitution at nucleotide position 986, causing the glycine (G) at amino acid position 329 to be replaced by an alanine (A). 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	Benign	0.11
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	0.071
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.97
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N;D
REVEL	Benign	0.12
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.047	D;D
Polyphen		1.0	D;.
Vest4		0.16
MutPred		0.14		Loss of catalytic residue at G329 (P = 0.0673);.;
MVP		0.66
MPC		0.28
ClinPred		0.82	D
GERP RS		3.2
Varity_R		0.14
gMVP		0.20
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.91
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs929539458; hg19: chr1-207082865;