1-206909788-G-T

Variant names:

• chr1-206909788-G-T
• rs760340568
• NM_005449.5:c.922C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005449.5(FCMR):​c.922C>A​(p.Pro308Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,448,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: FCMR NM_005449.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.986
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010482997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.922C>A	p.Pro308Thr	missense_variant	Exon 6 of 8	ENST00000367091.8	NP_005440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCMR	ENST00000367091.8	c.922C>A	p.Pro308Thr	missense_variant	Exon 6 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.000603

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000273 AC: 13 AN: 47552 AF XY: 0.000399

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000630

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000449 AC: 582 AN: 1296664 Hom.: 0 Cov.: 31 AF XY: 0.000443 AC XY: 282 AN XY: 637058

African (AFR) AF: 0.000119 AC: 3 AN: 25250

American (AMR) AF: 0.0000539 AC: 1 AN: 18538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21226

East Asian (EAS) AF: 0.00 AC: 0 AN: 28268

South Asian (SAS) AF: 0.00 AC: 0 AN: 66468

European-Finnish (FIN) AF: 0.0000272 AC: 1 AN: 36826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4738

European-Non Finnish (NFE) AF: 0.000535 AC: 557 AN: 1041726

Other (OTH) AF: 0.000373 AC: 20 AN: 53624

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74352

African (AFR) AF: 0.000121 AC: 5 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000422 Hom.: 0

Bravo AF: 0.000268

ExAC AF: 0.0000753 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.922C>A (p.P308T) alteration is located in exon 6 (coding exon 6) of the FCMR gene. This alteration results from a C to A substitution at nucleotide position 922, causing the proline (P) at amino acid position 308 to be replaced by a threonine (T). 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	-0.58	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.99
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;D
REVEL	Benign	0.059
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.068	T;T
Polyphen		0.84	P;.
Vest4		0.20
MVP		0.18
MPC		0.38
ClinPred		0.021	T
GERP RS		2.0
Varity_R		0.057
gMVP		0.17
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs760340568; hg19: chr1-207083133;