14-55350980-A-G

Position:

• chr14-55350980-A-G

Variant summary

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

The ENST00000313833.5(FBXO34):​c.590A>G​(p.Asp197Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXO34 ENST00000313833.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17192674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO34	NM_017943.4	c.590A>G	p.Asp197Gly	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.590A>G	p.Asp197Gly	missense_variant	2/2	1	NM_017943.4	ENSP00000313159	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

Apr 22, 2024

The c.590A>G (p.D197G) alteration is located in exon 2 (coding exon 1) of the FBXO34 gene. This alteration results from a A to G substitution at nucleotide position 590, causing the aspartic acid (D) at amino acid position 197 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.091
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.84	D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.094
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.21	B;B
Vest4		0.14
MutPred		0.31		Gain of catalytic residue at G196 (P = 0);Gain of catalytic residue at G196 (P = 0);
MVP		0.48
MPC		0.50
ClinPred		0.80	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.26

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: chr14-55817698;