rs587777703

Variant names:

• chr16-87335448-CAGGCA-T
• rs587777703
• NM_024735.5:c.847_852delTGCCTGinsA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_024735.5(FBXO31):​c.847_852delTGCCTGinsA​(p.Cys283AsnfsTer81) variant causes a frameshift, synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXO31 NM_024735.5 frameshift, synonymous
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.24
• Publications: 1 publications found

Genes affected

FBXO31 (HGNC:16510): (F-box protein 31) This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

FBXO31 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal recessive 45

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-87335448-CAGGCA-T is Pathogenic according to our data. Variant chr16-87335448-CAGGCA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 155905.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024735.5. 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
	FBXO31	NM_024735.5	MANE Select	c.847_852delTGCCTGinsA	p.Cys283AsnfsTer81	frameshift synonymous	Exon 7 of 9	NP_079011.3
	FBXO31	NM_001282683.2		c.331_336delTGCCTGinsA	p.Cys111AsnfsTer81	frameshift synonymous	Exon 8 of 10	NP_001269612.1	A0A0C4DGU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	ENST00000311635.12	TSL:1 MANE Select	c.847_852delTGCCTGinsA	p.Cys283AsnfsTer81	frameshift synonymous	Exon 7 of 9	ENSP00000310841.4	Q5XUX0-1
	FBXO31	ENST00000636077.2	TSL:5	c.934_939delTGCCTGinsA	p.Cys312AsnfsTer81	frameshift synonymous	Exon 8 of 10	ENSP00000490402.2	A0A1B0GV77
	FBXO31	ENST00000971306.1		c.931_936delTGCCTGinsA	p.Cys311AsnfsTer81	frameshift synonymous	Exon 8 of 10	ENSP00000641365.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual disability, autosomal recessive 45 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2
Mutation Taster		=2/198	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs587777703; hg19: chr16-87369054;