14-55350925-C-A

Position:

• chr14-55350925-C-A

Variant summary

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

The NM_017943.4(FBXO34):​c.535C>A​(p.Pro179Thr) 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: FBXO34 NM_017943.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15

Genes affected

FBXO34 (HGNC:20201): (F-box protein 34) Members of the F-box protein family, such as FBXO34, 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

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	UniProt
FBXO34	NM_017943.4	c.535C>A	p.Pro179Thr	missense_variant	2/2	ENST00000313833.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO34	ENST00000313833.5	c.535C>A	p.Pro179Thr	missense_variant	2/2	1	NM_017943.4	P1

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 24, 2022

The c.535C>A (p.P179T) alteration is located in exon 2 (coding exon 1) of the FBXO34 gene. This alteration results from a C to A substitution at nucleotide position 535, causing the proline (P) at amino acid position 179 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.99	D;D
Vest4		0.56
MutPred		0.44		Gain of catalytic residue at Q176 (P = 0);Gain of catalytic residue at Q176 (P = 0);
MVP		0.62
MPC		0.62
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.29

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: chr14-55817643;