dbSNP rs2108444091: FXR1:p.Ser27Tyr (chr3-180933362-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005087.4(FXR1):c.80C>A(p.Ser27Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,424,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S27C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FXR1
NM_005087.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.55

Publications

0 publications found

Variant links:

Genes affected

FXR1 (HGNC:4023): (FMR1 autosomal homolog 1) The protein encoded by this gene is an RNA binding protein that interacts with the functionally-similar proteins FMR1 and FXR2. These proteins shuttle between the nucleus and cytoplasm and associate with polyribosomes, predominantly with the 60S ribosomal subunit. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

FXR1 Gene-Disease associations (from GenCC):

congenital myopathy
Inheritance: AR Classification: STRONG Submitted by: G2P
myopathy, congenital, with respiratory insufficiency and bone fractures
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
myopathy, congenital proximal, with minicore lesions
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

FXR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXR1	NM_005087.4 link	c.80C>A	p.Ser27Tyr	missense_variant	Exon 2 of 17	ENST00000357559.9	NP_005078.2	P51114-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9 link	c.80C>A	p.Ser27Tyr	missense_variant	Exon 2 of 17	1	NM_005087.4	ENSP00000350170.3		P51114-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1424184

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710942

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32724

American (AMR)

AF:

0.00

AC:

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.00

AC:

AN:

85108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078236

Other (OTH)

AF:

0.00

AC:

AN:

59134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;.;T;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.6

M;M;.;.

PhyloP100

6.5

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

0.98

D;D;D;.

Vest4

0.78

MutPred

0.45

Gain of phosphorylation at S27 (P = 0.0545);Gain of phosphorylation at S27 (P = 0.0545);.;.;

MVP

0.55

MPC

2.4

ClinPred

0.98

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.54

Mutation Taster

=38/62

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over