NM_024735.5:c.490-7_490-5delCCT

Variant names:

• chr16-87343769-CAGG-C
• rs773844606
• NM_024735.5:c.490-7_490-5delCCT

Variant summary

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

The NM_024735.5(FBXO31):​c.490-7_490-5delCCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,614,090 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: FBXO31 NM_024735.5 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.280
• Publications: 0 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 0 ACMG points.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	NM_024735.5	MANE Select	c.490-7_490-5delCCT		splice_region intron	N/A	NP_079011.3
	FBXO31	NM_001282683.2		c.-27-7_-27-5delCCT		splice_region intron	N/A	NP_001269612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	ENST00000311635.12	TSL:1 MANE Select	c.490-7_490-5delCCT		splice_region intron	N/A	ENSP00000310841.4
	FBXO31	ENST00000636077.2	TSL:5	c.577-7_577-5delCCT		splice_region intron	N/A	ENSP00000490402.2
	FBXO31	ENST00000618298.6	TSL:5	c.-27-7_-27-5delCCT		splice_region intron	N/A	ENSP00000479703.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152256 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000288 AC: 72 AN: 250102 AF XY: 0.000222

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000524

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000293 AC: 429 AN: 1461716 Hom.: 1 AF XY: 0.000292 AC XY: 212 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26106

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000349 AC: 388 AN: 1111932

Other (OTH) AF: 0.000364 AC: 22 AN: 60390

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152374 Hom.: 0 Cov.: 34 AF XY: 0.000322 AC XY: 24 AN XY: 74514

African (AFR) AF: 0.0000240 AC: 1 AN: 41596

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68032

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000618 Hom.: 0

Bravo AF: 0.000291

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Apr 05, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Uncertain:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FBXO31: PM2, BP4

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs773844606; hg19: chr16-87377375;