2-73263766-G-C

Variant names:

• chr2-73263766-G-C
• NM_001371389.2:c.1987C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371389.2(FBXO41):​c.1987C>G​(p.Arg663Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXO41 NM_001371389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO41	NM_001371389.2	c.1987C>G	p.Arg663Gly	missense_variant	Exon 8 of 13	ENST00000520530.3	NP_001358318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO41	ENST00000520530.3	c.1987C>G	p.Arg663Gly	missense_variant	Exon 8 of 13	5	NM_001371389.2	ENSP00000430968.2
FBXO41	ENST00000295133.9	c.1987C>G	p.Arg663Gly	missense_variant	Exon 7 of 12	1		ENSP00000295133.6
FBXO41	ENST00000521871.5	c.1987C>G	p.Arg663Gly	missense_variant	Exon 8 of 13	5		ENSP00000428646.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1987C>G (p.R663G) alteration is located in exon 7 (coding exon 7) of the FBXO41 gene. This alteration results from a C to G substitution at nucleotide position 1987, causing the arginine (R) at amino acid position 663 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;.;.
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Benign	0.22
Sift	Benign	0.057	.;T;.
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.72
MutPred		0.57		Loss of stability (P = 0.0476);Loss of stability (P = 0.0476);Loss of stability (P = 0.0476);
MVP		0.45
MPC		0.63
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-73490894;