NM_005449.5:c.974C>T

Variant names:

• chr1-206909736-G-A
• rs773792868
• NM_005449.5:c.974C>T

Variant summary

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

The NM_005449.5(FCMR):​c.974C>T​(p.Ala325Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,301,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A325G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: FCMR NM_005449.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• 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=0.018155754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.974C>T	p.Ala325Val	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.974C>T	p.Ala325Val	missense_variant	Exon 6 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000127 AC: 7 AN: 54948 AF XY: 0.000214

Gnomad AFR exome AF: 0.00

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: 0.0000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000161 AC: 21 AN: 1301964 Hom.: 0 Cov.: 31 AF XY: 0.0000265 AC XY: 17 AN XY: 640546

African (AFR) AF: 0.00 AC: 0 AN: 25380

American (AMR) AF: 0.00 AC: 0 AN: 19842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21814

East Asian (EAS) AF: 0.00 AC: 0 AN: 28284

South Asian (SAS) AF: 0.000262 AC: 18 AN: 68684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4508

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1046542

Other (OTH) AF: 0.0000185 AC: 1 AN: 54064

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000702 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.018	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.26
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.015
Sift	Benign	0.18	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.029	B;.
Vest4		0.048
MutPred		0.12		Gain of catalytic residue at A325 (P = 0.0067);.;
MVP		0.055
MPC		0.22
ClinPred		0.054	T
GERP RS		0.84
Varity_R		0.030
gMVP		0.10
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs773792868; hg19: chr1-207083081;