chr2-73258990-C-T

Variant names:

• chr2-73258990-C-T
• rs199625082
• NM_001371389.2:c.2620G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371389.2(FBXO41):​c.2620G>A​(p.Gly874Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,581,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: FBXO41 NM_001371389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0439063).

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.2620G>A	p.Gly874Ser	missense	Exon 13 of 13	NP_001358318.1	Q8TF61
	FBXO41	NM_001080410.4		c.2620G>A	p.Gly874Ser	missense	Exon 17 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.2620G>A	p.Gly874Ser	missense	Exon 13 of 13	ENSP00000430968.2	Q8TF61
	FBXO41	ENST00000295133.9	TSL:1	c.2620G>A	p.Gly874Ser	missense	Exon 12 of 12	ENSP00000295133.6	Q8TF61
	FBXO41	ENST00000521871.5	TSL:5	c.2620G>A	p.Gly874Ser	missense	Exon 13 of 13	ENSP00000428646.1	Q8TF61

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000133 AC: 26 AN: 196122 AF XY: 0.000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000169

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000215

Gnomad OTH exome AF: 0.000200

GnomAD4 exome AF: 0.000162 AC: 232 AN: 1429334 Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 109 AN XY: 708150

African (AFR) AF: 0.0000308 AC: 1 AN: 32494

American (AMR) AF: 0.000173 AC: 7 AN: 40372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25480

East Asian (EAS) AF: 0.00 AC: 0 AN: 37468

South Asian (SAS) AF: 0.0000858 AC: 7 AN: 81560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.000195 AC: 214 AN: 1096236

Other (OTH) AF: 0.0000508 AC: 3 AN: 59062

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74362

African (AFR) AF: 0.000121 AC: 5 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000250 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.000266 AC: 1

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.000108 AC: 13

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	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.060
Sift	Benign	0.26	T
Sift4G	Benign	0.57	T
Polyphen		0.58	P
Vest4		0.061
MVP		0.20
MPC		0.84
ClinPred		0.10	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.19
Mutation Taster		=93/7	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: rs199625082; hg19: chr2-73486118;