14-55350983-G-C

Position:

• chr14-55350983-G-C

Variant summary

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

The NM_017943.4(FBXO34):​c.593G>C​(p.Gly198Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: FBXO34 NM_017943.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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]

FBXO34 (HGNC:):

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=0.105840206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO34	NM_017943.4	c.593G>C	p.Gly198Ala	missense_variant	2/2	ENST00000313833.5	NP_060413.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO34	ENST00000313833.5	c.593G>C	p.Gly198Ala	missense_variant	2/2	1	NM_017943.4	ENSP00000313159.4

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 18, 2024

The c.593G>C (p.G198A) alteration is located in exon 2 (coding exon 1) of the FBXO34 gene. This alteration results from a G to C substitution at nucleotide position 593, causing the glycine (G) at amino acid position 198 to be replaced by an alanine (A). 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	0.093
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.19
Sift	Benign	0.090	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.20	B;B
Vest4		0.11
MutPred		0.31		Gain of catalytic residue at D194 (P = 0);Gain of catalytic residue at D194 (P = 0);
MVP		0.54
MPC		0.16
ClinPred		0.90	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.061
gMVP		0.54

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: chr14-55817701;