3-180968173-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005087.4(FXR1):​c.1321C>T​(p.Arg441Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

FXR1
NM_005087.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
FXR1NM_005087.4 linkc.1321C>T p.Arg441Cys missense_variant Exon 14 of 17 ENST00000357559.9 NP_005078.2 P51114-1
FXR1NM_001013438.3 linkc.1321C>T p.Arg441Cys missense_variant Exon 14 of 16 NP_001013456.1 P51114-2
FXR1NM_001013439.3 linkc.1066C>T p.Arg356Cys missense_variant Exon 15 of 18 NP_001013457.1 P51114-3
FXR1NM_001363882.1 linkc.1066C>T p.Arg356Cys missense_variant Exon 15 of 17 NP_001350811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FXR1ENST00000357559.9 linkc.1321C>T p.Arg441Cys missense_variant Exon 14 of 17 1 NM_005087.4 ENSP00000350170.3 P51114-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251260
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461428
Hom.:
0
Cov.:
30
AF XY:
0.0000261
AC XY:
19
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1321C>T (p.R441C) alteration is located in exon 14 (coding exon 14) of the FXR1 gene. This alteration results from a C to T substitution at nucleotide position 1321, causing the arginine (R) at amino acid position 441 to be replaced by a cysteine (C). 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
Pathogenic
0.88
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.39
T;.;.;T;.;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D
MetaSVM
Benign
-0.68
T
MutationAssessor
Uncertain
2.5
M;.;.;.;M;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D;D
REVEL
Benign
0.26
Sift
Uncertain
0.0040
D;D;D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;D
Polyphen
1.0
D;.;D;D;D;D
Vest4
0.61
MVP
0.56
MPC
2.5
ClinPred
0.98
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.34
gMVP
0.53

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

LitVar

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

Other links and lift over

dbSNP: rs774705357; hg19: chr3-180685961; API