FBXW11 p.Arg518Arg

Variant names:

• chr5-171868772-G-G
• NM_001378974.1:c.

Your query was ambiguous. Multiple possible variants found:

• chr5-171868773--
• chr5-171868773-C-A
• chr5-171868773-C-G
• chr5-171868773-C-T
• chr5-171868775-G-T
• chr5-171868773-CCG-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001378974.1(FBXW11):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXW11 NM_001378974.1 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 0 publications found

Genes affected

FBXW11 (HGNC:13607): (F-box and WD repeat domain containing 11) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class and, in addition to an F-box, contains multiple WD40 repeats. This gene contains at least 14 exons, and its alternative splicing generates 3 transcript variants diverging at the presence/absence of two alternate exons. [provided by RefSeq, Jul 2008]

FBXW11 Gene-Disease associations (from GenCC):

• neurodevelopmental, jaw, eye, and digital syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378974.1. 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
	FBXW11	NM_001378974.1	MANE Select	c.		exon_region	Exon 13 of 14	NP_001365903.1	E5RGC1
	FBXW11	NM_012300.3		c.		exon_region	Exon 12 of 13	NP_036432.2
	FBXW11	NM_001378975.1		c.		exon_region	Exon 12 of 13	NP_001365904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXW11	ENST00000517395.6	TSL:3 MANE Select	c.		exon_region	Exon 13 of 14	ENSP00000428753.2	E5RGC1
	FBXW11	ENST00000265094.9	TSL:1	c.		exon_region	Exon 12 of 13	ENSP00000265094.5	Q9UKB1-1
	FBXW11	ENST00000296933.10	TSL:1	c.		exon_region	Exon 12 of 13	ENSP00000296933.6	Q9UKB1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.060

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-171295776;