9-37574568-T-C

Variant names:

• chr9-37574568-T-C
• rs10758441
• NM_012166.3:c.-7+1643A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012166.3. 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
	FBXO10	NM_012166.3	MANE Select	c.-7+1643A>G		intron	N/A	NP_036298.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO10	ENST00000432825.7	TSL:1 MANE Select	c.-7+1643A>G		intron	N/A	ENSP00000403802.2
	ENSG00000256966	ENST00000537239.2	TSL:5	n.*87+14243A>G		intron	N/A	ENSP00000457849.1
	ENSG00000256966	ENST00000541804.1	TSL:1	n.62+14245A>G		intron	N/A

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

African (AFR) AF: 0.770 AC: 31911 AN: 41452

American (AMR) AF: 0.769 AC: 11753 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2119 AN: 3464

East Asian (EAS) AF: 0.939 AC: 4847 AN: 5164

South Asian (SAS) AF: 0.769 AC: 3702 AN: 4812

European-Finnish (FIN) AF: 0.668 AC: 7042 AN: 10540

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44664 AN: 67960

Other (OTH) AF: 0.711 AC: 1498 AN: 2108

Alfa AF: 0.687 Hom.: 59765

Bravo AF: 0.727

Asia WGS AF: 0.844 AC: 2933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		0.25
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: rs10758441; hg19: chr9-37574565;