3-196577472-C-T

Variant names:

• chr3-196577472-C-T
• NM_001105573.2:c.338C>T

Variant summary

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

The NM_001105573.2(FBXO45):​c.338C>T​(p.Ala113Val) 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: 33)
• Consequence: FBXO45 NM_001105573.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

Genes affected

FBXO45 (HGNC:29148): (F-box protein 45) Members of the F-box protein family, such as FBXO45, 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 (summary by Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Jan 2011]

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 rank	MANE	Protein	UniProt
FBXO45	NM_001105573.2	c.338C>T	p.Ala113Val	missense_variant	Exon 2 of 3	ENST00000311630.7	NP_001099043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO45	ENST00000311630.7	c.338C>T	p.Ala113Val	missense_variant	Exon 2 of 3	1	NM_001105573.2	ENSP00000310332.6
FBXO45	ENST00000440469	c.-200C>T		5_prime_UTR_variant	Exon 2 of 3	2		ENSP00000389868.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.338C>T (p.A113V) alteration is located in exon 2 (coding exon 2) of the FBXO45 gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). 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	0.87
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.53		Loss of catalytic residue at A113 (P = 0.068);
MVP		0.53
MPC		2.1
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.37
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-196304343;