Genetic Variant FBXO36:p.Phe35Cys (chr2-229976248-T-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_174899.5(FBXO36):c.104T>G(p.Phe35Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 1,600,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FBXO36
NM_174899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33175665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO36	NM_174899.5 link	c.104T>G	p.Phe35Cys	missense_variant	Exon 2 of 4	ENST00000283946.8	NP_777559.3	Q8NEA4-1
FBXO36	XM_005246317.3 link	c.29T>G	p.Phe10Cys	missense_variant	Exon 2 of 4		XP_005246374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBXO36	ENST00000283946.8 link	c.104T>G	p.Phe35Cys	missense_variant	Exon 2 of 4	1	NM_174899.5	ENSP00000283946.3	Q8NEA4-1
FBXO36	ENST00000373652.7 link	c.11T>G	p.Phe4Cys	missense_variant	Exon 3 of 5	1		ENSP00000362756.3	Q8NEA4-3
FBXO36	ENST00000465090.2 link	n.127T>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
FBXO36	ENST00000409992.1 link	c.104T>G	p.Phe35Cys	missense_variant	Exon 2 of 4	5		ENSP00000386673.1	B8ZZQ1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000752

AC:

AN:

239410

AF XY:

0.0000387

show subpopulations

Gnomad AFR exome

AF:

0.00100

Gnomad AMR exome

AF:

0.0000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1447846

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720024

show subpopulations

African (AFR)

AF:

0.000427

AC:

AN:

32752

American (AMR)

AF:

0.0000483

AC:

AN:

41394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25548

East Asian (EAS)

AF:

0.00

AC:

AN:

39566

South Asian (SAS)

AF:

0.00

AC:

AN:

83096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106688

Other (OTH)

AF:

0.0000167

AC:

AN:

59830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000243

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.000845

AC:

AN:

41420

American (AMR)

AF:

0.000131

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000782

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.104T>G (p.F35C) alteration is located in exon 2 (coding exon 2) of the FBXO36 gene. This alteration results from a T to G substitution at nucleotide position 104, causing the phenylalanine (F) at amino acid position 35 to be replaced by a cysteine (C). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.83

T;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

.;M;.

PhyloP100

2.1

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.017

D;D;D

Sift4G

Uncertain

0.0070

D;D;T

Polyphen

1.0, 1.0

.;D;D

Vest4

0.70

MVP

0.63

MPC

0.35

ClinPred

0.27

GERP RS

4.6

Varity_R

0.17

gMVP

0.69

Mutation Taster

=80/20

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.

2-229976248-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over