Genetic Variant ENST00000409509.5:n.360G>T (chr16-67210101-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000409509.5(FBXL9P):n.360G>T 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 0.000000716 in 1,396,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FBXL9P
ENST00000409509.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

0 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: 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=0.1893563).

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.375G>T	non_coding_transcript_exon	Exon 3 of 7
FBXL9P	NR_172489.1	n.497G>T	non_coding_transcript_exon	Exon 3 of 7
FBXL9P	NR_172490.1	n.497G>T	non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
FBXL9P	ENST00000409509.5	TSL:1	n.360G>T	non_coding_transcript_exon	Exon 3 of 6
FBXL9P	ENST00000637247.2	TSL:1	n.561G>T	non_coding_transcript_exon	Exon 3 of 7
FBXL9P	ENST00000409037.6	TSL:5	n.1117G>T	non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1396082

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688348

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

31478

American (AMR)

AF:

0.00

AC:

AN:

35578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25148

East Asian (EAS)

AF:

0.00

AC:

AN:

35634

South Asian (SAS)

AF:

0.00

AC:

AN:

79026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4242

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077962

Other (OTH)

AF:

0.00

AC:

AN:

57764

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.375

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.10

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.48

M_CAP

Benign

0.019

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.084

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.027

Polyphen

0.99

Vest4

0.34

MutPred

0.42

Gain of MoRF binding (P = 0.06)

MVP

0.055

ClinPred

0.61

GERP RS

-0.53

Varity_R

0.076

gMVP

0.42

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

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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