chr1-206909520-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005449.5(FCMR):​c.986G>A​(p.Gly329Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 1,172,224 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. 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. G329A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: FCMR NM_005449.5 missense, splice_region
• Scores: Splicing: ADA: 0.9934
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.986G>A	p.Gly329Asp	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>A	p.Gly329Asp	missense_variant, splice_region_variant	Exon 7 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000427 AC: 5 AN: 1172224 Hom.: 0 Cov.: 30 AF XY: 0.00000534 AC XY: 3 AN XY: 562092

African (AFR) AF: 0.00 AC: 0 AN: 23408

American (AMR) AF: 0.000451 AC: 4 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: 0.00000103 AC: 1 AN: 972734

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	0.084
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.51	T
PhyloP100		0.97
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.050	T;T
Polyphen		1.0	D;.
Vest4		0.15
MutPred		0.14		Loss of MoRF binding (P = 0.066);.;
MVP		0.71
MPC		0.88
ClinPred		0.88	D
GERP RS		3.2
Varity_R		0.32
gMVP		0.23
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.060		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: rs929539458; hg19: chr1-207082865;