7-5500955-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024963.6(FBXL18):c.1314G>T(p.Gln438His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,386,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

FBXL18
NM_024963.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0390

Publications

0 publications found

Variant links:

Genes affected

FBXL18 (HGNC:21874): (F-box and leucine rich repeat protein 18) The protein encoded by this gene is a member of a family of proteins that contain an approximately 40-amino acid F-box motif. This motif is important for interaction with SKP1 and for targeting some proteins for degradation. The encoded protein has been shown to control the cellular level of FBXL7, a protein that induces mitotic arrest, by targeting it for polyubiquitylation and proteasomal degradation. Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [provided by RefSeq, Mar 2016]

FBXL18 links:

Genome browser will be placed here

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=0.13414529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL18	NM_024963.6 link	c.1314G>T	p.Gln438His	missense_variant	Exon 3 of 5	ENST00000382368.8	NP_079239.3	Q96ME1-4Q96D16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBXL18	ENST00000382368.8 link	c.1314G>T	p.Gln438His	missense_variant	Exon 3 of 5	5	NM_024963.6	ENSP00000371805.3	Q96ME1-4
FBXL18	ENST00000458142.1 link	c.963G>T	p.Gln321His	missense_variant	Exon 1 of 3	2		ENSP00000405896.1	A0A994ENR3
FBXL18	ENST00000415009.5 link	n.1314G>T		non_coding_transcript_exon_variant	Exon 3 of 7	2		ENSP00000415064.1	Q96ME1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000635

AC:

AN:

157458

AF XY:

0.0000115

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000138

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1386014

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

683546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31196

American (AMR)

AF:

0.00

AC:

AN:

31094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21982

East Asian (EAS)

AF:

0.00

AC:

AN:

38630

South Asian (SAS)

AF:

0.00

AC:

AN:

74876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1079244

Other (OTH)

AF:

0.00

AC:

AN:

57224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000113

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1314G>T (p.Q438H) alteration is located in exon 3 (coding exon 3) of the FBXL18 gene. This alteration results from a G to T substitution at nucleotide position 1314, causing the glutamine (Q) at amino acid position 438 to be replaced by a histidine (H). 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

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.7

(source)

DANN

Benign

0.60

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.74

M_CAP

Benign

0.025

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

-0.039

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.59

REVEL

Benign

0.068

Sift

Benign

0.18

Sift4G

Benign

0.12

Polyphen

0.59

Vest4

0.098

MutPred

0.13

Loss of helix (P = 0.079);

MVP

0.75

MPC

0.50

ClinPred

0.19

GERP RS

4.5

gMVP

0.30

Mutation Taster

=94/6

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over