Genetic Variant ENST00000360587.2:c.494G>C (chr15-63601436-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000360587.2(FBXL22):c.494G>C(p.Gly165Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,427,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

FBXL22
ENST00000360587.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.04

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047952235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360587.2. 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_203373.3		c.494G>C	p.Gly165Ala	missense	Exon 2 of 2	NP_976307.2	Q6P050
FBXL22	NM_001367809.1		c.*144G>C		3_prime_UTR	Exon 3 of 3	NP_001354738.1	H0YMQ4
FBXL22	NM_001367807.1	MANE Select	c.*397G>C		downstream_gene	N/A	NP_001354736.1	A0A1W2PQW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL22	ENST00000360587.2	TSL:1	c.494G>C	p.Gly165Ala	missense	Exon 2 of 2	ENSP00000353794.3	Q6P050
FBXL22	ENST00000560325.1	TSL:3	c.*144G>C		3_prime_UTR	Exon 3 of 3	ENSP00000473666.1	R4GNI3
USP3-AS1	ENST00000561256.5	TSL:3	n.154C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000141

AC:

AN:

212630

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000186

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000560

AC:

AN:

1427806

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32218

American (AMR)

AF:

0.00

AC:

AN:

41086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24722

East Asian (EAS)

AF:

0.000207

AC:

AN:

38732

South Asian (SAS)

AF:

0.00

AC:

AN:

83428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093836

Other (OTH)

AF:

0.00

AC:

AN:

58670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000167

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

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.2

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.37

M_CAP

Benign

0.0072

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-1.0

PrimateAI

Benign

0.47

REVEL

Benign

0.013

Sift4G

Benign

0.93

Vest4

0.085

MVP

0.26

MPC

0.20

ClinPred

0.23

GERP RS

-0.92

Varity_R

0.031

gMVP

0.076

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over