ENST00000440067.4:c.1577G>A

Variant names:

• chr7-102883386-C-T
• rs778713363
• ENST00000440067.4:c.1577G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000440067.4(FBXL13):​c.1577G>A​(p.Cys526Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C526F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBXL13 ENST00000440067.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL13	NM_001394494.2	c.1577G>A	p.Cys526Tyr	missense_variant	Exon 15 of 21		NP_001381423.1
FBXL13	NM_145032.3	c.1307G>A	p.Cys436Tyr	missense_variant	Exon 14 of 20		NP_659469.3
FBXL13	NM_001287150.2	c.1307G>A	p.Cys436Tyr	missense_variant	Exon 14 of 19		NP_001274079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4	c.1577G>A	p.Cys526Tyr	missense_variant	Exon 15 of 21	3		ENSP00000390126.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250610 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T;T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;.;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D
MetaSVM	Benign	-0.97	T
PhyloP100		5.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-9.1	D;D;D;.;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D;.;D
Sift4G	Uncertain	0.011	D;D;D;D;D
Polyphen		1.0	D;D;D;.;D
Vest4		0.86
MutPred		0.73		Gain of phosphorylation at C436 (P = 0.0293);Gain of phosphorylation at C436 (P = 0.0293);Gain of phosphorylation at C436 (P = 0.0293);.;Gain of phosphorylation at C436 (P = 0.0293);
MVP		0.53
MPC		0.64
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.82
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs778713363; hg19: chr7-102523833;