rs201247137

Variant names:

• chr3-180912721-C-T
• rs201247137
• NM_005087.4:c.36C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001013439.3(FXR1):​c.-564C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: FXR1 NM_001013439.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• congenital myopathy

  Inheritance: AR Classification: STRONG Submitted by: G2P
• myopathy, congenital, with respiratory insufficiency and bone fractures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• myopathy, congenital proximal, with minicore lesions

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000296167 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 3-180912721-C-T is Benign according to our data. Variant chr3-180912721-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2654294.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013439.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	NM_005087.4	MANE Select	c.36C>T	p.Asn12Asn	synonymous	Exon 1 of 17	NP_005078.2	P51114-1
	FXR1	NM_001013439.3		c.-564C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001013457.1	P51114-3
	FXR1	NM_001363882.1		c.-564C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001350811.1	E7EU85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	ENST00000357559.9	TSL:1 MANE Select	c.36C>T	p.Asn12Asn	synonymous	Exon 1 of 17	ENSP00000350170.3	P51114-1
	FXR1	ENST00000445140.6	TSL:1	c.36C>T	p.Asn12Asn	synonymous	Exon 1 of 16	ENSP00000388828.2	P51114-2
	FXR1	ENST00000305586.11	TSL:5	c.-564C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000307633.7	P51114-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251422 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461738 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111900

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		1.6
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201247137; hg19: chr3-180630509;