ENST00000440067.4:c.2320C>G

Variant names:

• chr7-102813500-G-C
• rs377759639
• ENST00000440067.4:c.2320C>G

Variant summary

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

The ENST00000440067.4(FBXL13):​c.2320C>G​(p.Gln774Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Q774K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXL13 ENST00000440067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986
• Publications: 1 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]

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

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=0.08390546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL13	NM_001394494.2	c.2320C>G	p.Gln774Glu	missense_variant	Exon 21 of 21		NP_001381423.1
FBXL13	NM_145032.3	c.2050C>G	p.Gln684Glu	missense_variant	Exon 20 of 20		NP_659469.3
FBXL13	NM_001287150.2	c.1966C>G	p.Gln656Glu	missense_variant	Exon 19 of 19		NP_001274079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4	c.2320C>G	p.Gln774Glu	missense_variant	Exon 21 of 21	3		ENSP00000390126.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0011	.;T;T;.;.
Eigen	Benign	-0.062
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.74	T;.;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.084	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.99
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.83	N;N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.49	T;T;T;D;T
Sift4G	Benign	0.33	T;T;T;D;T
Polyphen		0.20	B;B;B;P;B
Vest4		0.16
MutPred		0.32		.;Loss of MoRF binding (P = 0.0469);Loss of MoRF binding (P = 0.0469);.;.;
MVP		0.29
MPC		0.12
ClinPred		0.56	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.21
Mutation Taster		=84/16	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: rs377759639; hg19: chr7-102453947;