3-121621920-C-T

Variant names:

• chr3-121621920-C-T
• rs753621120
• NM_016298.4:c.491C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016298.4(FBXO40):​c.491C>T​(p.Thr164Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. T164N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXO40 NM_016298.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 0 publications found

Genes affected

FBXO40 (HGNC:29816): (F-box protein 40) Members of the F-box protein family, such as FBXO40, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05507025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016298.4. 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
	FBXO40	NM_016298.4	MANE Select	c.491C>T	p.Thr164Ile	missense	Exon 3 of 4	NP_057382.2	Q9UH90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO40	ENST00000338040.6	TSL:1 MANE Select	c.491C>T	p.Thr164Ile	missense	Exon 3 of 4	ENSP00000337510.4	Q9UH90
	FBXO40	ENST00000868808.1		c.491C>T	p.Thr164Ile	missense	Exon 4 of 5	ENSP00000538867.1
	FBXO40	ENST00000868809.1		c.491C>T	p.Thr164Ile	missense	Exon 4 of 5	ENSP00000538868.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.18
DANN	Benign	0.37
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.28
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.10
Sift	Benign	0.23	T
Sift4G	Benign	0.23	T
Polyphen		0.0020	B
Vest4		0.025
MutPred		0.33		Gain of sheet (P = 0.0028)
MVP		0.32
MPC		0.10
ClinPred		0.086	T
GERP RS		4.6
Varity_R		0.032
gMVP		0.18
Mutation Taster		=96/4	polymorphism

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: rs753621120; hg19: chr3-121340767;