rs11768465

chr7-100600763-C-Gchr7-100600763-C-T

Variant summary

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

The NM_033506.3(FBXO24):c.1607C>G(p.Thr536Arg) 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 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBXO24 NM_033506.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14

Genes affected

FBXO24 (HGNC:13595): (F-box protein 24) 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

PCOLCE-AS1 (HGNC:40430): (PCOLCE antisense RNA 1)

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=0.11445126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO24	NM_033506.3	c.1607C>G	p.Thr536Arg	missense_variant	10/10	ENST00000241071.11
PCOLCE-AS1	NR_038910.1	n.1182G>C		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO24	ENST00000241071.11	c.1607C>G	p.Thr536Arg	missense_variant	10/10	1	NM_033506.3	A2
PCOLCE-AS1	ENST00000442166.2	n.1182G>C		non_coding_transcript_exon_variant	4/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0077	T;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.42	N;N;N
REVEL	Benign	0.077
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.0050	B;.;.
Vest4		0.24
MutPred		0.27		Loss of phosphorylation at T536 (P = 0.0468);.;.;
MVP		0.35
MPC		0.37
ClinPred		0.71	D
GERP RS		3.1
Varity_R		0.10
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11768465; hg19: chr7-100198386;