Variant chr1-206909497-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005449.5(FCMR):c.1009G>A(p.Gly337Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000056 in 1,285,816 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 2 hom. )

Consequence

FCMR
NM_005449.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

Variant links:

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]

FCMR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03535652).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCMR	NM_005449.5 linkuse as main transcript	c.1009G>A	p.Gly337Ser	missense_variant	7/8	ENST00000367091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCMR	ENST00000367091.8 linkuse as main transcript	c.1009G>A	p.Gly337Ser	missense_variant	7/8	1	NM_005449.5	P2	O60667-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000582

AC:

AN:

1133576

Hom.:

Cov.:

AF XY:

0.0000629

AC XY:

AN XY:

540616

show subpopulations

Gnomad4 AFR exome

AF:

0.0000431

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000105

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000207

AC:

Asia WGS

AF:

0.00347

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.1009G>A (p.G337S) alteration is located in exon 7 (coding exon 7) of the FCMR gene. This alteration results from a G to A substitution at nucleotide position 1009, causing the glycine (G) at amino acid position 337 to be replaced by a serine (S). 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

0.090

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.3

DANN

Benign

0.97

DEOGEN2

Benign

0.051

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.016

Sift

Benign

0.36

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.024

B;.

Vest4

0.078

MutPred

0.087

Gain of glycosylation at G337 (P = 0.0012);.;

MVP

0.12

MPC

0.22

ClinPred

0.29

GERP RS

-0.96

Varity_R

0.037

gMVP

0.091

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over