NM_001371389.2:c.2306G>A

Variant names:

• chr2-73260532-C-T
• rs1687973863
• NM_001371389.2:c.2306G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001371389.2(FBXO41):​c.2306G>A​(p.Arg769Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,443,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: FBXO41 NM_001371389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.27
• Publications: 0 publications found

Genes affected

FBXO41 (HGNC:29409): (F-box protein 41) This gene encodes a member of the F-box protein family, which is characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one of the four subunits of the SCF ubiquitin protein ligase complex that plays a role in phosphorylation-dependent ubiquitination. F-box proteins are divided into three classes depending on the interaction substrate domain each contains in addition to the F-box motif: FBXW proteins contain WD-40 domains, FBXL proteins contain leucine-rich repeats, and FBXO proteins contain either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the FBXO class. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371389.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO41	NM_001371389.2	MANE Select	c.2306G>A	p.Arg769Gln	missense	Exon 11 of 13	NP_001358318.1	Q8TF61
	FBXO41	NM_001080410.4		c.2306G>A	p.Arg769Gln	missense	Exon 15 of 17	NP_001073879.2	Q8TF61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO41	ENST00000520530.3	TSL:5 MANE Select	c.2306G>A	p.Arg769Gln	missense	Exon 11 of 13	ENSP00000430968.2	Q8TF61
	FBXO41	ENST00000295133.9	TSL:1	c.2306G>A	p.Arg769Gln	missense	Exon 10 of 12	ENSP00000295133.6	Q8TF61
	FBXO41	ENST00000521871.5	TSL:5	c.2306G>A	p.Arg769Gln	missense	Exon 11 of 13	ENSP00000428646.1	Q8TF61

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000624 AC: 9 AN: 1443210 Hom.: 0 Cov.: 32 AF XY: 0.00000698 AC XY: 5 AN XY: 716194

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 42064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25718

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38638

South Asian (SAS) AF: 0.00 AC: 0 AN: 82982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000725 AC: 8 AN: 1103076

Other (OTH) AF: 0.00 AC: 0 AN: 59738

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.25
Sift	Benign	0.19	T
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.48		Loss of methylation at R765 (P = 0.0521)
MVP		0.52
MPC		0.35
ClinPred		0.89	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.50
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1687973863; hg19: chr2-73487660;