NM_033506.3:c.1607C>T

Variant names:

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

Variant summary

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

The NM_033506.3(FBXO24):​c.1607C>T​(p.Thr536Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,954 control chromosomes in the GnomAD database, including 42,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (5251 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37680 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00285393).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

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>T	p.Thr536Met	missense	Exon 10 of 10	NP_277041.1	A4D2D3
	FBXO24	NM_012172.5		c.1721C>T	p.Thr574Met	missense	Exon 10 of 10	NP_036304.2	O75426-3
	FBXO24	NM_001163499.2		c.1571C>T	p.Thr524Met	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>T	p.Thr536Met	missense	Exon 10 of 10	ENSP00000241071.6	O75426-1
	FBXO24	ENST00000488079.1	TSL:1	n.*882C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000418814.1	F8WC52
	FBXO24	ENST00000488079.1	TSL:1	n.*882C>T		3_prime_UTR	Exon 7 of 7	ENSP00000418814.1	F8WC52

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38053 AN: 152008 Hom.: 5227 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.215 AC: 54109 AN: 251396 AF XY: 0.217

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.0152

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.222 AC: 324322 AN: 1461828 Hom.: 37680 Cov.: 35 AF XY: 0.223 AC XY: 161869 AN XY: 727220

African (AFR) AF: 0.351 AC: 11763 AN: 33478

American (AMR) AF: 0.161 AC: 7199 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6221 AN: 26130

East Asian (EAS) AF: 0.0122 AC: 483 AN: 39700

South Asian (SAS) AF: 0.228 AC: 19666 AN: 86258

European-Finnish (FIN) AF: 0.259 AC: 13814 AN: 53412

Middle Eastern (MID) AF: 0.190 AC: 1098 AN: 5766

European-Non Finnish (NFE) AF: 0.225 AC: 250663 AN: 1111970

Other (OTH) AF: 0.222 AC: 13415 AN: 60396

GnomAD4 genome AF: 0.251 AC: 38116 AN: 152126 Hom.: 5251 Cov.: 32 AF XY: 0.247 AC XY: 18352 AN XY: 74370

African (AFR) AF: 0.347 AC: 14398 AN: 41486

American (AMR) AF: 0.177 AC: 2706 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3470

East Asian (EAS) AF: 0.0184 AC: 95 AN: 5170

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4826

European-Finnish (FIN) AF: 0.269 AC: 2846 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15477 AN: 67976

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.231 Hom.: 14755

Bravo AF: 0.249

TwinsUK AF: 0.222 AC: 825

ALSPAC AF: 0.220 AC: 847

ESP6500AA AF: 0.341 AC: 1502

ESP6500EA AF: 0.233 AC: 2001

ExAC AF: 0.223 AC: 27120

Asia WGS AF: 0.117 AC: 409 AN: 3478

EpiCase AF: 0.221

EpiControl AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.81	N
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.060
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MPC		0.33
ClinPred		0.0060	T
GERP RS		3.1
Varity_R		0.019
gMVP		0.39
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: rs11768465; hg19: chr7-100198386; COSMIC: COSV53826120; COSMIC: COSV53826120;