7-102877523-C-T

Variant names:

• chr7-102877523-C-T
• rs1563030177
• NM_001394494.2:c.1849G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394494.2(FBXL13):​c.1849G>A​(p.Val617Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,140 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: FBXL13 NM_001394494.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080972075).

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.1849G>A	p.Val617Ile	missense	Exon 17 of 21	NP_001381423.1	C9JI88
	FBXL13	NM_145032.3		c.1579G>A	p.Val527Ile	missense	Exon 16 of 20	NP_659469.3	Q8N1P0
	FBXL13	NM_001287150.2		c.1579G>A	p.Val527Ile	missense	Exon 16 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.1849G>A	p.Val617Ile	missense	Exon 17 of 21	ENSP00000390126.2	C9JI88
	FBXL13	ENST00000379305.7	TSL:1	n.*1578G>A		non_coding_transcript_exon	Exon 16 of 19	ENSP00000368607.4	A0A8V8NC12
	FBXL13	ENST00000448002.6	TSL:1	n.1849G>A		non_coding_transcript_exon	Exon 17 of 21	ENSP00000405434.2	E7ERH8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

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	Benign	0.085
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.68
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.022
Sift	Benign	0.045	D
Sift4G	Benign	0.19	T
Polyphen		0.024	B
Vest4		0.049
MutPred		0.48		Gain of catalytic residue at L532 (P = 0.0377)
MVP		0.19
MPC		0.076
ClinPred		0.034	T
GERP RS		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.073
gMVP		0.19
Mutation Taster		=97/3	polymorphism

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: rs1563030177; hg19: chr7-102517970;