7-102883386-C-A

Variant names:

• chr7-102883386-C-A
• rs778713363
• NM_001394494.2:c.1577G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001394494.2(FBXL13):​c.1577G>T​(p.Cys526Phe) variant causes a missense change. 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: 31)
• Consequence: FBXL13 NM_001394494.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL13	NM_001394494.2	MANE Select	c.1577G>T	p.Cys526Phe	missense	Exon 15 of 21	NP_001381423.1	C9JI88
	FBXL13	NM_145032.3		c.1307G>T	p.Cys436Phe	missense	Exon 14 of 20	NP_659469.3	Q8N1P0
	FBXL13	NM_001287150.2		c.1307G>T	p.Cys436Phe	missense	Exon 14 of 19	NP_001274079.1	Q8NEE6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL13	ENST00000440067.4	TSL:3 MANE Select	c.1577G>T	p.Cys526Phe	missense	Exon 15 of 21	ENSP00000390126.2	C9JI88
	FBXL13	ENST00000379305.7	TSL:1	n.*1306G>T		non_coding_transcript_exon	Exon 14 of 19	ENSP00000368607.4	A0A8V8NC12
	FBXL13	ENST00000448002.6	TSL:1	n.1577G>T		non_coding_transcript_exon	Exon 15 of 21	ENSP00000405434.2	E7ERH8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.97	T
PhyloP100		5.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-9.1	D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.79		Gain of ubiquitination at K437 (P = 0.0872)
MVP		0.60
MPC		0.61
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.96
gMVP		0.82
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs778713363; hg19: chr7-102523833;