Genetic Variant FBXL9P:n.328G>A (chr16-67210133-C-T) – 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 ENST00000409509.5(FBXL9P):n.328G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000557 in 1,550,260 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

FBXL9P
ENST00000409509.5 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

Publications

5 publications found

Variant links:

Genes affected

FBXL9P (HGNC:):

FBXL9P links:

FBXL9P (HGNC:13605): (F-box and leucine rich repeat protein, pseudogene) 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 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 Fbls class and, in addition to an F-box, contains 9 tandem leucine-rich repeats. Two transcript variants encoding the same protein have been found for this gene. Other variants may occur, but their full-length natures have not been characterized. [provided by RefSeq, Jul 2008]

FBXL9P 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=0.02302581).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409509.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
FBXL9P	NR_172488.1	n.343G>A	non_coding_transcript_exon	Exon 3 of 7
FBXL9P	NR_172489.1	n.465G>A	non_coding_transcript_exon	Exon 3 of 7
FBXL9P	NR_172490.1	n.465G>A	non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
FBXL9P	ENST00000409509.5	TSL:1	n.328G>A	non_coding_transcript_exon	Exon 3 of 6
FBXL9P	ENST00000637247.2	TSL:1	n.529G>A	non_coding_transcript_exon	Exon 3 of 7
FBXL9P	ENST00000409037.6	TSL:5	n.1085G>A	non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152252

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:

0.000603

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000236

AC:

AN:

157004

AF XY:

0.000217

show subpopulations

Gnomad AFR exome

AF:

0.000112

Gnomad AMR exome

AF:

0.0000403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000528

Gnomad OTH exome

AF:

0.000679

GnomAD4 exome

AF:

0.000588

AC:

822

AN:

1398008

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

375

AN XY:

689594

show subpopulations

African (AFR)

AF:

0.0000949

AC:

AN:

31602

American (AMR)

AF:

0.0000559

AC:

AN:

35788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25150

East Asian (EAS)

AF:

0.00

AC:

AN:

35816

South Asian (SAS)

AF:

0.00

AC:

AN:

79162

European-Finnish (FIN)

AF:

0.000163

AC:

AN:

49182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4298

European-Non Finnish (NFE)

AF:

0.000731

AC:

789

AN:

1079150

Other (OTH)

AF:

0.000346

AC:

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.000276

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.000727

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000234

AC:

ESP6500EA

AF:

0.000358

AC:

ExAC

AF:

0.0000578

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

0.092

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.079

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00033

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.47

M_CAP

Benign

0.0048

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

-1.3

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.32

REVEL

Benign

0.041

Sift

Benign

0.24

Sift4G

Benign

0.33

Polyphen

0.026

Vest4

0.10

MVP

0.25

ClinPred

0.034

GERP RS

1.1

Varity_R

0.032

gMVP

0.14

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over