rs10758440

chr9-37573333-A-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+2878T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,078 control chromosomes in the GnomAD database, including 3,491 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 0.20 (3491 hom., cov: 31)
• Consequence: FBXO10 NM_012166.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO10	NM_012166.3	c.-7+2878T>G		intron_variant		ENST00000432825.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO10	ENST00000432825.7	c.-7+2878T>G		intron_variant		1	NM_012166.3	P1
FBXO10	ENST00000541607.1	c.-7+2189T>G		intron_variant		2
FBXO10	ENST00000276960.7	c.-7+2878T>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30913 AN: 151960 Hom.: 3484 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.204 AC: 30948 AN: 152078 Hom.: 3491 Cov.: 31 AF XY: 0.205 AC XY: 15258 AN XY: 74344

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.187

Alfa AF: 0.225 Hom.: 5393

Bravo AF: 0.197

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
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: rs10758440; hg19: chr9-37573330;