2-229976295-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_174899.5(FBXO36):c.151C>T(p.Pro51Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00586 in 1,613,518 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 38 hom. )

Consequence

FBXO36
NM_174899.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.81

Publications

11 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0110967755).

BP6

Variant 2-229976295-C-T is Benign according to our data. Variant chr2-229976295-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651989.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00598 (8738/1461308) while in subpopulation MID AF = 0.0255 (147/5766). AF 95% confidence interval is 0.0221. There are 38 homozygotes in GnomAdExome4. There are 4343 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO36	NM_174899.5 link	c.151C>T	p.Pro51Ser	missense_variant	Exon 2 of 4	ENST00000283946.8	NP_777559.3	Q8NEA4-1
FBXO36	XM_005246317.3 link	c.76C>T	p.Pro26Ser	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.151C>T	p.Pro51Ser	missense_variant	Exon 2 of 4	1	NM_174899.5	ENSP00000283946.3	Q8NEA4-1
FBXO36	ENST00000373652.7 link	c.58C>T	p.Pro20Ser	missense_variant	Exon 3 of 5	1		ENSP00000362756.3	Q8NEA4-3
FBXO36	ENST00000465090.2 link	n.174C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
FBXO36	ENST00000409992.1 link	c.151C>T	p.Pro51Ser	missense_variant	Exon 2 of 4	5		ENSP00000386673.1	B8ZZQ1

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

725

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00728

Gnomad OTH

AF:

0.00958

GnomAD2 exomes

AF:

0.00489

AC:

1229

AN:

251162

AF XY:

0.00506

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00714

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00598

AC:

8738

AN:

1461308

Hom.:

Cov.:

AF XY:

0.00597

AC XY:

4343

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

33462

American (AMR)

AF:

0.00450

AC:

201

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

241

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39618

South Asian (SAS)

AF:

0.00276

AC:

238

AN:

86224

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.0255

AC:

147

AN:

5766

European-Non Finnish (NFE)

AF:

0.00670

AC:

7451

AN:

1111636

Other (OTH)

AF:

0.00558

AC:

337

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

387

773

1160

1546

1933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00476

AC:

724

AN:

152210

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

325

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41542

American (AMR)

AF:

0.00412

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00728

AC:

495

AN:

68000

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00496

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00476

AC:

578

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.00853

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FBXO36: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

.;T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Uncertain

0.40

MutationAssessor

Uncertain

2.8

.;M;.

PhyloP100

4.8

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.9

D;D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.69

MVP

0.94

MPC

0.33

ClinPred

0.025

GERP RS

5.7

Varity_R

0.84

gMVP

0.77

Mutation Taster

=99/1

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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2-229976295-C-T

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