3-180971083-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_005087.4(FXR1):c.1603+733dup variant causes a intron change. The variant allele was found at a frequency of 0.000109 in 1,228,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: FXR1 NM_005087.4 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.22

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
• PP5: Variant 3-180971083-G-GA is Pathogenic according to our data. Variant chr3-180971083-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 2443948.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXR1	NM_005087.4	c.1603+733dup		intron_variant		ENST00000357559.9
FXR1	NM_001013438.3	c.1603+733dup		intron_variant
FXR1	NM_001013439.3	c.1348+733dup		intron_variant
FXR1	NM_001363882.1	c.1348+733dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXR1	ENST00000357559.9	c.1603+733dup		intron_variant		1	NM_005087.4

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151556 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000120 AC: 129 AN: 1077432 Hom.: 0 Cov.: 20 AF XY: 0.000131 AC XY: 69 AN XY: 527534

Gnomad4 AFR exome AF: 0.000132

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000854

Gnomad4 SAS exome AF: 0.000249

Gnomad4 FIN exome AF: 0.0000867

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.0000777

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151556 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73978

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Myopathy, congenital proximal, with minicore lesions Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 13, 2023

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Computational scores

Source: dbNSFP v4.3

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: rs769011065; hg19: chr3-180688871;