13-77025819-T-C

Variant names:

• chr13-77025819-T-C
• rs700361
• NM_012158.4:c.-2+1008A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012158.4(FBXL3):​c.-2+1008A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,000 control chromosomes in the GnomAD database, including 7,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (7863 hom., cov: 32)
• Consequence: FBXL3 NM_012158.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 3 publications found

Genes affected

FBXL3 (HGNC:13599): (F-box and leucine rich repeat protein 3) 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 Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats and is localized in the nucleus. [provided by RefSeq, Jul 2008]

FBXL3 Gene-Disease associations (from GenCC):

• intellectual disability, short stature, facial anomalies, and joint dislocations

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000283208 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012158.4. 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
	FBXL3	NM_012158.4	MANE Select	c.-2+1008A>G		intron	N/A	NP_036290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL3	ENST00000355619.10	TSL:1 MANE Select	c.-2+1008A>G		intron	N/A	ENSP00000347834.5
	ENSG00000283208	ENST00000638147.2	TSL:5	c.565+29692T>C		intron	N/A	ENSP00000490953.2
	FBXL3	ENST00000885159.1		c.-2+1193A>G		intron	N/A	ENSP00000555218.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36484 AN: 151882 Hom.: 7828 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.241 AC: 36587 AN: 152000 Hom.: 7863 Cov.: 32 AF XY: 0.239 AC XY: 17766 AN XY: 74304

African (AFR) AF: 0.574 AC: 23785 AN: 41418

American (AMR) AF: 0.218 AC: 3334 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5178

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4826

European-Finnish (FIN) AF: 0.0930 AC: 979 AN: 10530

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.0844 AC: 5736 AN: 67986

Other (OTH) AF: 0.202 AC: 426 AN: 2110

Alfa AF: 0.121 Hom.: 1555

Bravo AF: 0.266

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.73
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs700361; hg19: chr13-77599954;