3-180933362-C-G

Position:

• chr3-180933362-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001013439.3(FXR1):​c.-176C>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FXR1 NM_001013439.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXR1	NM_005087.4	c.80C>G	p.Ser27Cys	missense_variant	2/17	ENST00000357559.9	NP_005078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9	c.80C>G	p.Ser27Cys	missense_variant	2/17	1	NM_005087.4	ENSP00000350170.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Scoliosis;C1837658:Delayed gross motor development;C4281993:Neonatal respiratory distress Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Jan 12, 2022

ACMG classification criteria: PM2 moderate, PP2 supporting, PP4 supporting, BP4 supporting -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;.;T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.6	M;M;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.032	D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.98	D;D;D;.
Vest4		0.68
MutPred		0.52		Gain of catalytic residue at L28 (P = 0.0154);Gain of catalytic residue at L28 (P = 0.0154);.;.;
MVP		0.55
MPC		2.1
ClinPred		0.97	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-180651150;