Genetic Variant NM_024963.6:c.*1225_*1226delAA (chr7-5480548-ATT-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is . The variant received 0 ACMG points: 0P and 0B.

The NM_024963.6(FBXL18):c.*1225_*1226delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

FBXL18
NM_024963.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.248

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:

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new If you want to explore the variant's impact on the transcript NM_024963.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024963.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FBXL18	NM_024963.6	MANE Select	c.1225_1226delAA	3_prime_UTR	Exon 5 of 5	NP_079239.3
FBXL18	NM_001367780.1		c.1225_1226delAA	3_prime_UTR	Exon 5 of 5	NP_001354709.1
FBXL18	NM_001367781.1		c.1225_1226delAA	3_prime_UTR	Exon 5 of 5	NP_001354710.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FBXL18	ENST00000382368.8	TSL:5 MANE Select	c.1225_1226delAA	3_prime_UTR	Exon 5 of 5	ENSP00000371805.3	Q96ME1-4
FBXL18	ENST00000948868.1		c.1225_1226delAA	splice_region	Exon 4 of 4	ENSP00000618927.1
FBXL18	ENST00000948868.1		c.1225_1226delAA	3_prime_UTR	Exon 4 of 4	ENSP00000618927.1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

AN:

40014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.0165

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000665

Gnomad OTH

AF:

0.00188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00160

AC:

AN:

40004

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

17854

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00234

AC:

AN:

10278

American (AMR)

AF:

0.00150

AC:

AN:

2662

Ashkenazi Jewish (ASJ)

AF:

0.0165

AC:

AN:

1214

East Asian (EAS)

AF:

0.00

AC:

AN:

1848

South Asian (SAS)

AF:

0.00

AC:

AN:

1160

European-Finnish (FIN)

AF:

0.00108

AC:

AN:

926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000665

AC:

AN:

21038

Other (OTH)

AF:

0.00187

AC:

AN:

536

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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NM_024963.6:c.1225_1226delAA

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