Genetic Variant FBXL13:p.Met716Ile (chr7-102822180-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394494.2(FBXL13):c.2148G>C(p.Met716Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FBXL13
NM_001394494.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.305

Publications

0 publications found

Variant links:

Genes affected

FBXL13 (HGNC:21658): (F-box and leucine rich repeat protein 13) Members of the F-box protein family, such as FBXL13, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

FBXL13 links:

ENSG00000302818 (HGNC:):

ENSG00000302818 links:

FAM185A (HGNC:22412): (family with sequence similarity 185 member A)

FAM185A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030341744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394494.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL13	NM_001394494.2	MANE Select	c.2148G>C	p.Met716Ile	missense	Exon 20 of 21	NP_001381423.1	C9JI88
FBXL13	NM_145032.3		c.1878G>C	p.Met626Ile	missense	Exon 19 of 20	NP_659469.3	Q8N1P0
FBXL13	NM_001287150.2		c.1794G>C	p.Met598Ile	missense	Exon 18 of 19	NP_001274079.1	Q8NEE6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL13	ENST00000440067.4	TSL:3 MANE Select	c.2148G>C	p.Met716Ile	missense	Exon 20 of 21	ENSP00000390126.2	C9JI88
FBXL13	ENST00000379305.7	TSL:1	n.*1793G>C		non_coding_transcript_exon	Exon 18 of 19	ENSP00000368607.4	A0A8V8NC12
FBXL13	ENST00000448002.6	TSL:1	n.*16G>C		non_coding_transcript_exon	Exon 20 of 21	ENSP00000405434.2	E7ERH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251140

AF XY:

0.00

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111950

Other (OTH)

AF:

0.00

AC:

AN:

60386

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.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.6

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.00053

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.49

M_CAP

Benign

0.0041

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

PhyloP100

-0.30

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.70

REVEL

Benign

0.081

Sift

Benign

0.36

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.17

MutPred

0.37

Loss of helix (P = 0.1299)

MVP

0.13

MPC

0.10

ClinPred

0.075

GERP RS

0.43

Varity_R

0.061

gMVP

0.27

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over