NM_005087.4:c.997G>A

Variant names:

• chr3-180961474-G-A
• NM_005087.4:c.997G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005087.4(FXR1):​c.997G>A​(p.Val333Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,359,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: FXR1 NM_005087.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3866496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXR1	NM_005087.4	c.997G>A	p.Val333Ile	missense_variant	Exon 11 of 17	ENST00000357559.9	NP_005078.2
FXR1	NM_001013438.3	c.997G>A	p.Val333Ile	missense_variant	Exon 11 of 16		NP_001013456.1
FXR1	NM_001013439.3	c.742G>A	p.Val248Ile	missense_variant	Exon 12 of 18		NP_001013457.1
FXR1	NM_001363882.1	c.742G>A	p.Val248Ile	missense_variant	Exon 12 of 17		NP_001350811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9	c.997G>A	p.Val333Ile	missense_variant	Exon 11 of 17	1	NM_005087.4	ENSP00000350170.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1359204 Hom.: 0 Cov.: 24 AF XY: 0.00000147 AC XY: 1 AN XY: 681570

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: 9.80e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;T;.;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	2.9	M;.;.;.;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.93	N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.040	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.72	P;.;B;B;D;D
Vest4		0.43
MutPred		0.74		Loss of disorder (P = 0.1818);.;.;.;Loss of disorder (P = 0.1818);.;
MVP		0.53
MPC		2.0
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.20
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-180679262;