6-145805283-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032145.5(FBXO30):​c.1123G>A​(p.Val375Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,724 control chromosomes in the GnomAD database, including 132,955 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.36 (10369 hom., cov: 33)
  • Exomes 𝑓: 0.41 (122586 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1279214E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO30	NM_032145.5	c.1123G>A	p.Val375Met	missense_variant	Exon 2 of 3	ENST00000237281.5	NP_115521.3
FBXO30	NM_001348092.2	c.1123G>A	p.Val375Met	missense_variant	Exon 2 of 3		NP_001335021.1
FBXO30	XM_047419398.1	c.1231G>A	p.Val411Met	missense_variant	Exon 2 of 3		XP_047275354.1
EPM2A-DT	NR_038246.1	n.53-23078C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO30	ENST00000237281.5	c.1123G>A	p.Val375Met	missense_variant	Exon 2 of 3	1	NM_032145.5	ENSP00000237281.3
EPM2A-DT	ENST00000629681.1	n.91-4495C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54383 AN: 151974 Hom.: 10356 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.380 AC: 95461 AN: 251026 AF XY: 0.396

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.246

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.388

GnomAD4 exome AF: 0.405 AC: 592142 AN: 1461630 Hom.: 122586 Cov.: 58 AF XY: 0.409 AC XY: 297535 AN XY: 727112

African (AFR) AF: 0.249 AC: 8331 AN: 33466

American (AMR) AF: 0.221 AC: 9870 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10120 AN: 26126

East Asian (EAS) AF: 0.265 AC: 10519 AN: 39692

South Asian (SAS) AF: 0.481 AC: 41445 AN: 86250

European-Finnish (FIN) AF: 0.481 AC: 25667 AN: 53398

Middle Eastern (MID) AF: 0.398 AC: 2293 AN: 5768

European-Non Finnish (NFE) AF: 0.414 AC: 459954 AN: 1111864

Other (OTH) AF: 0.396 AC: 23943 AN: 60392

GnomAD4 genome AF: 0.358 AC: 54414 AN: 152094 Hom.: 10369 Cov.: 33 AF XY: 0.361 AC XY: 26854 AN XY: 74352

African (AFR) AF: 0.248 AC: 10278 AN: 41482

American (AMR) AF: 0.285 AC: 4361 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1337 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1334 AN: 5164

South Asian (SAS) AF: 0.478 AC: 2307 AN: 4822

European-Finnish (FIN) AF: 0.493 AC: 5225 AN: 10588

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.416 AC: 28279 AN: 67972

Other (OTH) AF: 0.358 AC: 755 AN: 2110

Alfa AF: 0.385 Hom.: 40432

Bravo AF: 0.335

TwinsUK AF: 0.422 AC: 1565

ALSPAC AF: 0.416 AC: 1604

ESP6500AA AF: 0.254 AC: 1117

ESP6500EA AF: 0.413 AC: 3553

ExAC AF: 0.390 AC: 47294

Asia WGS AF: 0.394 AC: 1369 AN: 3478

EpiCase AF: 0.417

EpiControl AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.3
DANN	Benign	0.71
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.00011	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.23
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.082
Sift	Benign	0.056	T
Sift4G	Benign	0.13	T
Polyphen		0.043	B
Vest4		0.14
MPC		0.23
ClinPred		0.0016	T
GERP RS		-3.2
Varity_R		0.039
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52790407;