Variant 3-180949288-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005087.4(FXR1):c.575T>C(p.Ile192Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FXR1
NM_005087.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

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 links:

FXR1 (HGNC:):

FXR1 links:

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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/exons	MANE	Protein	UniProt
FXR1	NM_005087.4 linkuse as main transcript	c.575T>C	p.Ile192Thr	missense_variant	7/17	ENST00000357559.9	NP_005078.2	P51114-1
FXR1	NM_001013438.3 linkuse as main transcript	c.575T>C	p.Ile192Thr	missense_variant	7/16		NP_001013456.1	P51114-2
FXR1	NM_001013439.3 linkuse as main transcript	c.320T>C	p.Ile107Thr	missense_variant	8/18		NP_001013457.1	P51114-3
FXR1	NM_001363882.1 linkuse as main transcript	c.320T>C	p.Ile107Thr	missense_variant	8/17		NP_001350811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9 linkuse as main transcript	c.575T>C	p.Ile192Thr	missense_variant	7/17	1	NM_005087.4	ENSP00000350170.3		P51114-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453454

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723724

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Jun 02, 2023

The c.575T>C (p.I192T) alteration is located in exon 7 (coding exon 7) of the FXR1 gene. This alteration results from a T to C substitution at nucleotide position 575, causing the isoleucine (I) at amino acid position 192 to be replaced by a threonine (T). 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

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;D;.;.;T;.;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.3

.;M;.;.;.;M;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D;D

Polyphen

0.81, 0.76, 0.69, 0.91

.;P;.;P;P;P;.;P

Vest4

0.72, 0.74, 0.68, 0.74, 0.71, 0.70

MutPred

0.56

.;Loss of stability (P = 0.0055);.;.;.;Loss of stability (P = 0.0055);.;.;

MVP

0.58

MPC

1.8

ClinPred

0.97

GERP RS

5.4

Varity_R

0.50

gMVP

0.80

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.

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