rs748830200

Variant names:

• chr2-73265402-C-T
• rs748830200
• NM_001371389.2:c.1444G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-73265402-C-T
• chr2-73265402-C-A

Variant summary

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

The NM_001371389.2(FBXO41):​c.1444G>A​(p.Glu482Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,594 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FBXO41 NM_001371389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17
• Publications: 1 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.1444G>A	p.Glu482Lys	missense	Exon 5 of 13	NP_001358318.1	Q8TF61
	FBXO41	NM_001080410.4		c.1444G>A	p.Glu482Lys	missense	Exon 9 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.1444G>A	p.Glu482Lys	missense	Exon 5 of 13	ENSP00000430968.2	Q8TF61
	FBXO41	ENST00000295133.9	TSL:1	c.1444G>A	p.Glu482Lys	missense	Exon 4 of 12	ENSP00000295133.6	Q8TF61
	FBXO41	ENST00000521871.5	TSL:5	c.1444G>A	p.Glu482Lys	missense	Exon 5 of 13	ENSP00000428646.1	Q8TF61

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244694 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725824

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111716

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 33

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 provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.025	D
Sift4G	Benign	0.093	T
Polyphen		0.95	P
Vest4		0.67
MutPred		0.13		Gain of ubiquitination at E482 (P = 0.0039)
MVP		0.29
MPC		0.67
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.46
Mutation Taster		=69/31	polymorphism

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: rs748830200; hg19: chr2-73492530;