7-102926299-T-G

Position:

• chr7-102926299-T-G

Variant summary

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

The NM_001394494.2(FBXL13):​c.1123A>C​(p.Asn375His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.33

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]

LRRC17 (HGNC:16895): (leucine rich repeat containing 17) Predicted to be involved in bone marrow development and negative regulation of osteoclast differentiation. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

FBXL13 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC17	NM_001031692.3	c.-140-7475T>G		intron_variant		ENST00000339431.9	NP_001026862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4	c.1123A>C	p.Asn375His	missense_variant	11/21	3		ENSP00000390126.2
LRRC17	ENST00000339431.9	c.-140-7475T>G		intron_variant		1	NM_001031692.3	ENSP00000344242.4

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.853A>C (p.N285H) alteration is located in exon 10 (coding exon 8) of the FBXL13 gene. This alteration results from a A to C substitution at nucleotide position 853, causing the asparagine (N) at amino acid position 285 to be replaced by a histidine (H). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	.;T;T;.;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;.;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.69	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.2	D;D;D;D;.;D
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D;D;D;D;.;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;D
Vest4		0.75
MutPred		0.49		Gain of catalytic residue at N285 (P = 0.0314);Gain of catalytic residue at N285 (P = 0.0314);Gain of catalytic residue at N285 (P = 0.0314);Gain of catalytic residue at N285 (P = 0.0314);.;Gain of catalytic residue at N285 (P = 0.0314);
MVP		0.24
MPC		0.49
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.39
gMVP		0.61

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102566746;