NM_005087.4:c.27C>T

Variant names:

• chr3-180912712-C-T
• rs1805578
• NM_005087.4:c.27C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005087.4(FXR1):​c.27C>T​(p.Arg9Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00574 in 1,613,834 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (230 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (205 hom.)
• Consequence: FXR1 NM_005087.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0850
• Publications: 2 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 3-180912712-C-T is Benign according to our data. Variant chr3-180912712-C-T is described in ClinVar as Benign. ClinVar VariationId is 791961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.085 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005087.4. 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.27C>T	p.Arg9Arg	synonymous	Exon 1 of 17	NP_005078.2	P51114-1
	FXR1	NM_001441509.1		c.27C>T	p.Arg9Arg	synonymous	Exon 1 of 17	NP_001428438.1
	FXR1	NM_001441510.1		c.27C>T	p.Arg9Arg	synonymous	Exon 1 of 16	NP_001428439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	ENST00000357559.9	TSL:1 MANE Select	c.27C>T	p.Arg9Arg	synonymous	Exon 1 of 17	ENSP00000350170.3	P51114-1
	FXR1	ENST00000445140.6	TSL:1	c.27C>T	p.Arg9Arg	synonymous	Exon 1 of 16	ENSP00000388828.2	P51114-2
	FXR1	ENST00000963215.1		c.27C>T	p.Arg9Arg	synonymous	Exon 1 of 17	ENSP00000633274.1

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4511 AN: 151914 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0192

GnomAD2 exomes AF: 0.00798 AC: 2006 AN: 251426 AF XY: 0.00575

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00581

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.000528

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00324 AC: 4742 AN: 1461804 Hom.: 205 Cov.: 34 AF XY: 0.00282 AC XY: 2049 AN XY: 727220

African (AFR) AF: 0.108 AC: 3627 AN: 33476

American (AMR) AF: 0.00637 AC: 285 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00134 AC: 35 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86254

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53420

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5768

European-Non Finnish (NFE) AF: 0.000308 AC: 342 AN: 1111934

Other (OTH) AF: 0.00644 AC: 389 AN: 60394

GnomAD4 genome AF: 0.0297 AC: 4516 AN: 152030 Hom.: 230 Cov.: 32 AF XY: 0.0287 AC XY: 2134 AN XY: 74308

African (AFR) AF: 0.104 AC: 4289 AN: 41436

American (AMR) AF: 0.00916 AC: 140 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67996

Other (OTH) AF: 0.0190 AC: 40 AN: 2102

Alfa AF: 0.0102 Hom.: 94

Bravo AF: 0.0340

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		-0.085
PromoterAI		0.0040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1805578; hg19: chr3-180630500; COSMIC: COSV59764939; COSMIC: COSV59764939;