7-102813419-T-C

Variant names:

• chr7-102813419-T-C
• ENST00000440067.4:c.2401A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394494.2(FBXL13):​c.2401A>G​(p.Asn801Asp) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXL13 NM_001394494.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.19

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071234524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL13	NM_001394494.2	c.2401A>G	p.Asn801Asp	missense_variant	Exon 21 of 21		NP_001381423.1
FBXL13	NM_145032.3	c.2131A>G	p.Asn711Asp	missense_variant	Exon 20 of 20		NP_659469.3
FBXL13	NM_001287150.2	c.2047A>G	p.Asn683Asp	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.2401A>G	p.Asn801Asp	missense_variant	Exon 21 of 21	3		ENSP00000390126.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2131A>G (p.N711D) alteration is located in exon 20 (coding exon 18) of the FBXL13 gene. This alteration results from a A to G substitution at nucleotide position 2131, causing the asparagine (N) at amino acid position 711 to be replaced by an aspartic acid (D). 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	Benign	0.056
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.011
DANN	Benign	0.95
DEOGEN2	Benign	0.0039	.;T;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.59	T;.;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.071	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.73	N;N;N;N;N
REVEL	Benign	0.013
Sift	Benign	0.10	T;T;T;D;T
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.13
MutPred		0.37		.;Loss of catalytic residue at N711 (P = 0.0093);Loss of catalytic residue at N711 (P = 0.0093);.;.;
MVP		0.12
MPC		0.11
ClinPred		0.094	T
GERP RS		-6.2
Varity_R		0.036
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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.

Other links and lift over

hg19: chr7-102453866;