rs587777703

Positions:

• chr16-87335447-TCAGGCA-TT

Variant summary

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

The NM_024735.5(FBXO31):​c.847_852delinsA​(p.Cys283AsnfsTer81) variant causes a frameshift 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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 155905.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO31	NM_024735.5	c.847_852delinsA	p.Cys283AsnfsTer81	frameshift_variant	7/9	ENST00000311635.12
FBXO31	NM_001282683.2	c.331_336delinsA	p.Cys111AsnfsTer81	frameshift_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO31	ENST00000311635.12	c.847_852delinsA	p.Cys283AsnfsTer81	frameshift_variant	7/9	1	NM_024735.5	P1
FBXO31	ENST00000618298.6	c.331_336delinsA	p.Cys111AsnfsTer81	frameshift_variant	7/9	5
FBXO31	ENST00000636077.2	c.934_939delinsA	p.Cys312AsnfsTer81	frameshift_variant	8/10	5
FBXO31	ENST00000565593.1	c.288-1332_288-1327delinsA		intron_variant, NMD_transcript_variant		5

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal recessive 45 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777703; hg19: chr16-87369054;