15-75917386-C-T

Position:

chr15-75917386-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_147188.3(FBXO22):c.620C>T(p.Thr207Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,579,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

FBXO22
NM_147188.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

FBXO22 (HGNC:13593): (F-box protein 22) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and, as a transcriptional target of the tumor protein p53, is thought to be involved in degradation of specific proteins in response to p53 induction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

FBXO22 links:

FBXO22 (HGNC:):

FBXO22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035450667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO22	NM_147188.3 linkuse as main transcript	c.620C>T	p.Thr207Ile	missense_variant	5/7	ENST00000308275.8	NP_671717.1	Q8NEZ5-1
FBXO22	NM_012170.4 linkuse as main transcript	c.620C>T	p.Thr207Ile	missense_variant	5/6		NP_036302.1	Q8NEZ5-3
FBXO22	XM_047432382.1 linkuse as main transcript	c.308C>T	p.Thr103Ile	missense_variant	4/6		XP_047288338.1
FBXO22	NR_037623.2 linkuse as main transcript	n.567C>T		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO22	ENST00000308275.8 linkuse as main transcript	c.620C>T	p.Thr207Ile	missense_variant	5/7	1	NM_147188.3	ENSP00000307833.3		Q8NEZ5-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.00143

GnomAD3 exomes

AF:

0.000143

AC:

AN:

237026

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

128988

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000364

AC:

AN:

1427404

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

711320

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.000987

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000643

Gnomad4 OTH exome

AF:

0.0000676

GnomAD4 genome

AF:

0.000230

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.0000885

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.620C>T (p.T207I) alteration is located in exon 5 (coding exon 5) of the FBXO22 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the threonine (T) at amino acid position 207 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

N;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.024

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.12

MutPred

0.36

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);.;

MVP

0.068

MPC

0.44

ClinPred

0.044

GERP RS

3.4

Varity_R

0.052

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over