13-77025819-T-C

Position:

• chr13-77025819-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXL3	NM_012158.4	c.-2+1008A>G		intron_variant		ENST00000355619.10	NP_036290.1
FBXL3	XM_005266336.2	c.-2+1193A>G		intron_variant			XP_005266393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL3	ENST00000355619.10	c.-2+1008A>G		intron_variant		1	NM_012158.4	ENSP00000347834	P1
FBXL3	ENST00000417323.1	c.-2+1008A>G		intron_variant		5		ENSP00000412183
FBXL3	ENST00000472949.1	n.259+1008A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.0972

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.202

Alfa AF: 0.115 Hom.: 1022

Bravo AF: 0.266

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs700361; hg19: chr13-77599954;