9-37574568-T-C

Position:

• chr9-37574568-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012166.3(FBXO10):​c.-7+1643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 151,980 control chromosomes in the GnomAD database, including 39,098 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 0.71 (39098 hom., cov: 31)
• Consequence: FBXO10 NM_012166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

Genes affected

FBXO10 (HGNC:13589): (F-box protein 10) Members of the F-box protein family, such as FBXO10, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ENSG00000256966 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO10	NM_012166.3	c.-7+1643A>G		intron_variant		ENST00000432825.7	NP_036298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO10	ENST00000432825.7	c.-7+1643A>G		intron_variant		1	NM_012166.3	ENSP00000403802.2
ENSG00000256966	ENST00000537239.2	n.*87+14243A>G		intron_variant		5		ENSP00000457849.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108298 AN: 151862 Hom.: 39032 Cov.: 31

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.713 AC: 108427 AN: 151980 Hom.: 39098 Cov.: 31 AF XY: 0.717 AC XY: 53286 AN XY: 74290

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.711

Alfa AF: 0.671 Hom.: 5567

Bravo AF: 0.727

Asia WGS AF: 0.844 AC: 2933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.85

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: rs10758441; hg19: chr9-37574565;