rs371936172

Variant names:

• chr6-53073581-C-G
• rs371936172
• NM_033480.3:c.191C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-53073581-C-G
• chr6-53073581-C-T

Variant summary

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

The NM_033480.3(FBXO9):​c.191C>G​(p.Ser64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000913 in 1,610,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S64F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: FBXO9 NM_033480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

Genes affected

FBXO9 (HGNC:13588): (F-box protein 9) 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. Alternative splicing of this gene generates at least 3 transcript variants diverging at the 5' terminus. [provided by RefSeq, Jul 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=0.20646876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO9	NM_033480.3	c.191C>G	p.Ser64Cys	missense_variant	Exon 3 of 13	ENST00000323557.12	NP_258441.1
FBXO9	NM_012347.4	c.221C>G	p.Ser74Cys	missense_variant	Exon 2 of 12		NP_036479.1
FBXO9	NM_033481.3	c.89C>G	p.Ser30Cys	missense_variant	Exon 3 of 13		NP_258442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO9	ENST00000323557.12	c.191C>G	p.Ser64Cys	missense_variant	Exon 3 of 13	1	NM_033480.3	ENSP00000326968.7
FBXO9	ENST00000244426.10	c.221C>G	p.Ser74Cys	missense_variant	Exon 2 of 12	1		ENSP00000244426.6
FBXO9	ENST00000370939.7	c.89C>G	p.Ser30Cys	missense_variant	Exon 3 of 13	1		ENSP00000359977.3
FBXO9	ENST00000498744.5	c.89C>G	p.Ser30Cys	missense_variant	Exon 4 of 7	3		ENSP00000418858.1
FBXO9	ENST00000473337.6	c.89C>G	p.Ser30Cys	missense_variant	Exon 3 of 6	4		ENSP00000420536.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000289 AC: 7 AN: 242494 Hom.: 0 AF XY: 0.0000457 AC XY: 6 AN XY: 131374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000641

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000994 AC: 145 AN: 1458610 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 78 AN XY: 725208

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000120

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74404

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000331 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.022	.;T;.;.;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.54	T;T;T;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.90	.;.;.;.;.;L
PROVEAN	Uncertain	-3.7	D;N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.10	T;T;T;T;T;T
Sift4G	Uncertain	0.020	D;T;T;T;T;T
Polyphen		0.73, 0.56	.;.;.;P;.;P
Vest4		0.11, 0.12
MVP		0.48
MPC		0.39
ClinPred		0.22	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
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

LitVar

Other links and lift over

dbSNP: rs371936172; hg19: chr6-52938379;