Genetic Variant FBXL22:p.Ser94Asn (chr15-63597673-G-A) – 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_001367807.1(FBXL22):c.281G>A(p.Ser94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,604,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

FBXL22
NM_001367807.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Publications

0 publications found

Variant links:

Genes affected

FBXL22 (HGNC:27537): (F-box and leucine rich repeat protein 22) This gene encodes a member of the F-box protein family. This F-box protein interacts with S-phase kinase-associated protein 1A and cullin in order to form SCF complexes which function as ubiquitin ligases.[provided by RefSeq, Sep 2010]

FBXL22 links:

USP3-AS1 (HGNC:44140): (USP3 antisense RNA 1)

USP3-AS1 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=0.17566362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367807.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL22	NM_001367807.1	MANE Select	c.281G>A	p.Ser94Asn	missense	Exon 1 of 2	NP_001354736.1	A0A1W2PQW8
FBXL22	NM_203373.3		c.281G>A	p.Ser94Asn	missense	Exon 1 of 2	NP_976307.2	Q6P050
FBXL22	NM_001367808.1		c.281G>A	p.Ser94Asn	missense	Exon 1 of 2	NP_001354737.1	H0YMQ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL22	ENST00000638704.2	TSL:2 MANE Select	c.281G>A	p.Ser94Asn	missense	Exon 1 of 2	ENSP00000492359.1	A0A1W2PQW8
FBXL22	ENST00000360587.2	TSL:1	c.281G>A	p.Ser94Asn	missense	Exon 1 of 2	ENSP00000353794.3	Q6P050
USP3-AS1	ENST00000558831.5	TSL:1	n.173-2887C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000807

AC:

AN:

247906

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000617

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:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000269

AC:

AN:

1452488

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

720848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39462

South Asian (SAS)

AF:

0.00

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000335

AC:

AN:

1105472

Other (OTH)

AF:

0.0000334

AC:

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

Eigen

Benign

0.078

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.77

M_CAP

Benign

0.0033

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

2.4

PrimateAI

Benign

0.41

REVEL

Benign

0.056

Sift4G

Benign

0.11

Vest4

0.049

MVP

0.33

MPC

0.21

ClinPred

0.64

GERP RS

4.7

PromoterAI

0.039

Neutral

(source)

Varity_R

0.12

gMVP

0.25

Mutation Taster

=90/10

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over