7-100600763-C-G

Variant names:

• chr7-100600763-C-G
• rs11768465
• NM_033506.3:c.1607C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T536M) has been classified as Uncertain significance.

• 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
• Publications: 35 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11445126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033506.3. 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
	FBXO24	NM_033506.3	MANE Select	c.1607C>G	p.Thr536Arg	missense	Exon 10 of 10	NP_277041.1	A4D2D3
	FBXO24	NM_012172.5		c.1721C>G	p.Thr574Arg	missense	Exon 10 of 10	NP_036304.2	O75426-3
	FBXO24	NM_001163499.2		c.1571C>G	p.Thr524Arg	missense	Exon 10 of 10	NP_001156971.1	O75426-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO24	ENST00000241071.11	TSL:1 MANE Select	c.1607C>G	p.Thr536Arg	missense	Exon 10 of 10	ENSP00000241071.6	O75426-1
	FBXO24	ENST00000488079.1	TSL:1	n.*882C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000418814.1	F8WC52
	FBXO24	ENST00000488079.1	TSL:1	n.*882C>G		3_prime_UTR	Exon 7 of 7	ENSP00000418814.1	F8WC52

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.077
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.017	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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs11768465; hg19: chr7-100198386;