6-145804764-T-C

Position:

• chr6-145804764-T-C

Variant summary

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

The NM_032145.5(FBXO30):​c.1642A>G​(p.Asn548Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXO30 NM_032145.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

Genes affected

FBXO30 (HGNC:15600): (F-box protein 30) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it is upregulated in nasopharyngeal carcinoma. [provided by RefSeq, Jul 2008]

EPM2A-DT (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
FBXO30	NM_032145.5	c.1642A>G	p.Asn548Asp	missense_variant	2/3	ENST00000237281.5	NP_115521.3
FBXO30	NM_001348092.2	c.1642A>G	p.Asn548Asp	missense_variant	2/3		NP_001335021.1
FBXO30	XM_047419398.1	c.1750A>G	p.Asn584Asp	missense_variant	2/3		XP_047275354.1
EPM2A-DT	NR_038246.1	n.53-23597T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO30	ENST00000237281.5	c.1642A>G	p.Asn548Asp	missense_variant	2/3	1	NM_032145.5	ENSP00000237281.3
EPM2A-DT	ENST00000629681.1	n.91-5014T>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 33

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

Nov 14, 2024

The c.1642A>G (p.N548D) alteration is located in exon 2 (coding exon 1) of the FBXO30 gene. This alteration results from a A to G substitution at nucleotide position 1642, causing the asparagine (N) at amino acid position 548 to be replaced by an aspartic acid (D). 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	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.18
Sift	Benign	0.054	T
Sift4G	Benign	0.083	T
Polyphen		0.37	B
Vest4		0.86
MutPred		0.56		Gain of catalytic residue at N548 (P = 0.0555);
MVP		0.20
MPC		0.75
ClinPred		0.92	D
GERP RS		5.9
Varity_R		0.45
gMVP		0.77

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: chr6-146125900;