rs1577005361
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001441509.1(FXR1):c.1764_1767delACAG(p.Arg588SerfsTer37) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000539 in 1,113,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000054 ( 0 hom. )
Consequence
FXR1
NM_001441509.1 frameshift
NM_001441509.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.79
Publications
0 publications found
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 myopathyInheritance: AR Classification: STRONG Submitted by: G2P
- myopathy, congenital, with respiratory insufficiency and bone fracturesInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- myopathy, congenital proximal, with minicore lesionsInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-180971145-TAGAC-T is Pathogenic according to our data. Variant chr3-180971145-TAGAC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 828056.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001441509.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FXR1 | NM_005087.4 | MANE Select | c.1603+790_1603+793delACAG | intron | N/A | NP_005078.2 | P51114-1 | ||
| FXR1 | NM_001441509.1 | c.1764_1767delACAG | p.Arg588SerfsTer37 | frameshift | Exon 15 of 17 | NP_001428438.1 | |||
| FXR1 | NM_001441512.1 | c.1677_1680delACAG | p.Arg559SerfsTer37 | frameshift | Exon 16 of 18 | NP_001428441.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FXR1 | ENST00000357559.9 | TSL:1 MANE Select | c.1603+790_1603+793delACAG | intron | N/A | ENSP00000350170.3 | P51114-1 | ||
| FXR1 | ENST00000445140.6 | TSL:1 | c.1603+790_1603+793delACAG | intron | N/A | ENSP00000388828.2 | P51114-2 | ||
| FXR1 | ENST00000963215.1 | c.1764_1767delACAG | p.Arg588SerfsTer35 | frameshift | Exon 15 of 17 | ENSP00000633274.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 0.00000539 AC: 6AN: 1113656Hom.: 0 AF XY: 0.00000732 AC XY: 4AN XY: 546452 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
6
AN:
1113656
Hom.:
AF XY:
AC XY:
4
AN XY:
546452
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
2
AN:
23430
American (AMR)
AF:
AC:
0
AN:
25206
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
15336
East Asian (EAS)
AF:
AC:
0
AN:
12634
South Asian (SAS)
AF:
AC:
0
AN:
73856
European-Finnish (FIN)
AF:
AC:
1
AN:
12754
Middle Eastern (MID)
AF:
AC:
0
AN:
4208
European-Non Finnish (NFE)
AF:
AC:
3
AN:
905682
Other (OTH)
AF:
AC:
0
AN:
40550
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0203910), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.383
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
30
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Myopathy, congenital, with respiratory insufficiency and bone fractures (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.