3-180971145-TAGAC-T

Variant summary

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

The NM_005087.4(FXR1):c.1603+790_1603+793del variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000539 in 1,113,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: FXR1 NM_005087.4 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.79

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 3-180971145-TAGAC-T is Pathogenic according to our data. Variant chr3-180971145-TAGAC-T is described in ClinVar as [Pathogenic]. Clinvar id is 828056.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-180971145-TAGAC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXR1	NM_005087.4	c.1603+790_1603+793del		intron_variant		ENST00000357559.9
FXR1	NM_001013438.3	c.1603+790_1603+793del		intron_variant
FXR1	NM_001013439.3	c.1348+790_1348+793del		intron_variant
FXR1	NM_001363882.1	c.1348+790_1348+793del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXR1	ENST00000357559.9	c.1603+790_1603+793del		intron_variant		1	NM_005087.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000539 AC: 6 AN: 1113656 Hom.: 0 AF XY: 0.00000732 AC XY: 4 AN XY: 546452

Gnomad4 AFR exome AF: 0.0000854

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: 0.0000784

Gnomad4 NFE exome AF: 0.00000331

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Myopathy, congenital, with respiratory insufficiency and bone fractures 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: rs1577005361; hg19: chr3-180688933;