rs9373475

Variant names:

• chr6-145805283-C-A
• rs9373475
• NM_032145.5:c.1123G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-145805283-C-A
• chr6-145805283-C-G
• chr6-145805283-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032145.5(FBXO30):​c.1123G>T​(p.Val375Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBXO30 NM_032145.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 36 publications found

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:48990): (EPM2A divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020950168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032145.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO30	NM_032145.5	MANE Select	c.1123G>T	p.Val375Leu	missense	Exon 2 of 3	NP_115521.3
	FBXO30	NM_001348092.2		c.1123G>T	p.Val375Leu	missense	Exon 2 of 3	NP_001335021.1	Q8TB52
	EPM2A-DT	NR_038246.1		n.53-23078C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO30	ENST00000237281.5	TSL:1 MANE Select	c.1123G>T	p.Val375Leu	missense	Exon 2 of 3	ENSP00000237281.3	Q8TB52
	FBXO30	ENST00000894020.1		c.1123G>T	p.Val375Leu	missense	Exon 2 of 3	ENSP00000564079.1
	FBXO30	ENST00000894021.1		c.1123G>T	p.Val375Leu	missense	Exon 2 of 3	ENSP00000564080.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461732 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 40432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.063
DANN	Benign	0.33
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.23
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.075
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.081
MutPred		0.17		Loss of methylation at K376 (P = 0.0424)
MVP		0.043
MPC		0.22
ClinPred		0.034	T
GERP RS		-3.2
Varity_R		0.044
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs9373475; hg19: chr6-146126419;