Genetic Variant FBXO33:p.Asn343Thr (chr14-39401544-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203301.4(FBXO33):c.1028A>C(p.Asn343Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N343S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FBXO33
NM_203301.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98

Publications

1 publications found

Variant links:

Genes affected

FBXO33 (HGNC:19833): (F-box protein 33) This locus represents an member of the F-box gene family. The encoded protein contains an F-box motif and a domain that might form a structure similar to a leucine-rich repeat found in placental RNAse inhibitor. This locus may be associated with copy number variation of UGT2B17 (GeneID 7367), which has been associated with susceptibility to osteoporosis.[provided by RefSeq, Sep 2010]

FBXO33 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14512974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203301.4. 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
	FBXO33	NM_203301.4	MANE Select	c.1028A>C	p.Asn343Thr	missense	Exon 3 of 4	NP_976046.1	Q7Z6M2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXO33	ENST00000298097.8	TSL:1 MANE Select	c.1028A>C	p.Asn343Thr	missense	Exon 3 of 4	ENSP00000298097.7	Q7Z6M2
FBXO33	ENST00000934503.1		c.874+154A>C		intron	N/A	ENSP00000604562.1
FBXO33	ENST00000554190.1	TSL:3	c.216-1757A>C		intron	N/A	ENSP00000451277.1	G3V3J7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251478

AF XY:

0.00000736

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.044

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

M_CAP

Benign

0.049

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.4

PhyloP100

3.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

REVEL

Benign

0.23

Sift

Uncertain

0.011

Sift4G

Benign

0.099

Polyphen

0.48

Vest4

0.28

MutPred

0.41

Gain of sheet (P = 0.0149)

MVP

0.068

MPC

0.26

ClinPred

0.24

GERP RS

4.7

Varity_R

0.098

gMVP

0.39

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over