rs1239912088

Variant names:

• chr2-73260845-G-T
• rs1239912088
• NM_001371389.2:c.2185C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-73260845-G-T
• chr2-73260845-G-A
• chr2-73260845-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001371389.2(FBXO41):​c.2185C>A​(p.Arg729Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,410,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R729H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: FBXO41 NM_001371389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

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.2185C>A	p.Arg729Ser	missense	Exon 10 of 13	NP_001358318.1	Q8TF61
	FBXO41	NM_001080410.4		c.2185C>A	p.Arg729Ser	missense	Exon 14 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.2185C>A	p.Arg729Ser	missense	Exon 10 of 13	ENSP00000430968.2	Q8TF61
	FBXO41	ENST00000295133.9	TSL:1	c.2185C>A	p.Arg729Ser	missense	Exon 9 of 12	ENSP00000295133.6	Q8TF61
	FBXO41	ENST00000521871.5	TSL:5	c.2185C>A	p.Arg729Ser	missense	Exon 10 of 13	ENSP00000428646.1	Q8TF61

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000425 AC: 6 AN: 1410834 Hom.: 0 Cov.: 31 AF XY: 0.00000574 AC XY: 4 AN XY: 696848

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.00 AC: 0 AN: 37150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25316

East Asian (EAS) AF: 0.00 AC: 0 AN: 37294

South Asian (SAS) AF: 0.00 AC: 0 AN: 80088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000553 AC: 6 AN: 1084520

Other (OTH) AF: 0.00 AC: 0 AN: 58456

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.27
Sift	Uncertain	0.023	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.89
MutPred		0.54		Loss of MoRF binding (P = 0.0131)
MVP		0.61
MPC		0.62
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.47
gMVP		0.67
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1239912088; hg19: chr2-73487973;