Genetic Variant FBXO36:p.Gln70Arg (chr2-229996754-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_174899.5(FBXO36):c.209A>G(p.Gln70Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FBXO36
NM_174899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Publications

0 publications found

Variant links:

Genes affected

FBXO36 (HGNC:27020): (F-box protein 36) Members of the F-box protein family, such as FBXO36, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXO36 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
FBXO36	NM_174899.5 link	c.209A>G	p.Gln70Arg	missense_variant	Exon 3 of 4	ENST00000283946.8	NP_777559.3	Q8NEA4-1
FBXO36	XM_005246317.3 link	c.134A>G	p.Gln45Arg	missense_variant	Exon 3 of 4		XP_005246374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBXO36	ENST00000283946.8 link	c.209A>G	p.Gln70Arg	missense_variant	Exon 3 of 4	1	NM_174899.5	ENSP00000283946.3	Q8NEA4-1
FBXO36	ENST00000373652.7 link	c.116A>G	p.Gln39Arg	missense_variant	Exon 4 of 5	1		ENSP00000362756.3	Q8NEA4-3
FBXO36	ENST00000409992.1 link	c.206-57A>G		intron_variant	Intron 2 of 3	5		ENSP00000386673.1	B8ZZQ1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454052

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33242

American (AMR)

AF:

0.00

AC:

AN:

43806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.00

AC:

AN:

84358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4366

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109238

Other (OTH)

AF:

0.0000167

AC:

AN:

60056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 26, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.209A>G (p.Q70R) alteration is located in exon 3 (coding exon 3) of the FBXO36 gene. This alteration results from a A to G substitution at nucleotide position 209, causing the glutamine (Q) at amino acid position 70 to be replaced by an arginine (R). 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

Benign

0.20

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.5

.;M

PhyloP100

5.2

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.99

.;D

Vest4

0.49

MutPred

0.52

.;Gain of sheet (P = 0.0477);

MVP

0.62

MPC

0.091

ClinPred

0.95

GERP RS

5.4

Varity_R

0.22

gMVP

0.43

Mutation Taster

=79/21

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

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2-229996754-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over