chr3-180912713-G-C

Variant names:

• chr3-180912713-G-C
• rs1457094206
• NM_005087.4:c.28G>C

Variant summary

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

The NM_005087.4(FXR1):​c.28G>C​(p.Gly10Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FXR1 NM_005087.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

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]

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, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXR1	NM_005087.4	c.28G>C	p.Gly10Arg	missense_variant	Exon 1 of 17	ENST00000357559.9	NP_005078.2
FXR1	NM_001013438.3	c.28G>C	p.Gly10Arg	missense_variant	Exon 1 of 16		NP_001013456.1
FXR1	NM_001013439.3	c.-572G>C		5_prime_UTR_variant	Exon 1 of 18		NP_001013457.1
FXR1	NM_001363882.1	c.-572G>C		5_prime_UTR_variant	Exon 1 of 17		NP_001350811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9	c.28G>C	p.Gly10Arg	missense_variant	Exon 1 of 17	1	NM_005087.4	ENSP00000350170.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.61	D;.;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	0.99	D;.;T;D
M_CAP	Pathogenic	0.51	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	-0.0026	T
MutationAssessor	Uncertain	2.8	M;.;.;M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.3	D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0050	D;.;D;D
Sift4G	Uncertain	0.025	D;.;D;D
Polyphen		0.67	P;.;D;D
Vest4		0.56
MutPred		0.65		Loss of methylation at R9 (P = 0.0401);Loss of methylation at R9 (P = 0.0401);Loss of methylation at R9 (P = 0.0401);Loss of methylation at R9 (P = 0.0401);
MVP		0.74
MPC		2.3
ClinPred		1.0	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.70

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

Other links and lift over

dbSNP: rs1457094206; hg19: chr3-180630501;