Variant 5-108020943-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000542267.7(FBXL17):c.1804T>C(p.Cys602Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FBXL17
ENST00000542267.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

Variant links:

Genes affected

FBXL17 (HGNC:13615): (F-box and leucine rich repeat protein 17) Members of the F-box protein family, such as FBXL17, 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]

FBXL17 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FBXL17	NM_001163315.3 linkuse as main transcript	c.1804T>C	p.Cys602Arg	missense_variant	7/9	ENST00000542267.7	NP_001156787.2
FBXL17	XM_005272048.5 linkuse as main transcript	c.1804T>C	p.Cys602Arg	missense_variant	7/8		XP_005272105.1
FBXL17	XM_011543574.4 linkuse as main transcript	c.1804T>C	p.Cys602Arg	missense_variant	7/8		XP_011541876.1
FBXL17	XM_011543575.3 linkuse as main transcript	c.1804T>C	p.Cys602Arg	missense_variant	7/8		XP_011541877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7 linkuse as main transcript	c.1804T>C	p.Cys602Arg	missense_variant	7/9	1	NM_001163315.3	ENSP00000437464	P1	Q9UF56-1
FBXL17	ENST00000496714.2 linkuse as main transcript	c.814T>C	p.Cys272Arg	missense_variant	6/7	1		ENSP00000418111
FBXL17	ENST00000481160.1 linkuse as main transcript	n.460T>C		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725078

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.1804T>C (p.C602R) alteration is located in exon 7 (coding exon 7) of the FBXL17 gene. This alteration results from a T to C substitution at nucleotide position 1804, causing the cysteine (C) at amino acid position 602 to be replaced by an arginine (R). 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

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;T;.;.

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.97

D;D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

3.0

.;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-7.7

D;D;.;D

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0, 1.0

.;D;.;D

Vest4

0.98

MutPred

0.87

.;Loss of stability (P = 0.0131);.;.;

MVP

0.62

MPC

2.2

ClinPred

1.0

GERP RS

5.5

Varity_R

0.99

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over