10-5903152-C-G

Variant names:

• chr10-5903152-C-G
• rs776902652
• NM_178150.3:c.134C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178150.3(FBH1):​c.134C>G​(p.Pro45Arg) 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. 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. P45L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBH1 NM_178150.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 1 publications found

Genes affected

FBH1 (HGNC:13620): (F-box DNA helicase 1) This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three 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 Fbx class. It contains an F-box motif and seven conserved helicase motifs, and has both DNA-dependent ATPase and DNA unwinding activities. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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=0.15504062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178150.3. 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
	FBH1	NM_178150.3	MANE Select	c.134C>G	p.Pro45Arg	missense	Exon 2 of 21	NP_835363.1	Q8NFZ0-1
	FBH1	NM_032807.5		c.287C>G	p.Pro96Arg	missense	Exon 3 of 22	NP_116196.3
	FBH1	NM_001258452.2		c.-89C>G		5_prime_UTR	Exon 2 of 22	NP_001245381.1	F6UZG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBH1	ENST00000362091.9	TSL:1 MANE Select	c.134C>G	p.Pro45Arg	missense	Exon 2 of 21	ENSP00000355415.4	Q8NFZ0-1
	FBH1	ENST00000379999.6	TSL:1	c.287C>G	p.Pro96Arg	missense	Exon 3 of 22	ENSP00000369335.5	Q8NFZ0-2
	FBH1	ENST00000908866.1		c.134C>G	p.Pro45Arg	missense	Exon 2 of 22	ENSP00000578925.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.0059
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.74	T
PhyloP100		0.41
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.036
Sift	Benign	0.18	T
Sift4G	Benign	0.15	T
Polyphen		0.43	B
Vest4		0.48
MutPred		0.34		Gain of MoRF binding (P = 0.0066)
MVP		0.068
MPC		0.18
ClinPred		0.66	D
GERP RS		4.5
Varity_R		0.089
gMVP		0.18
Mutation Taster		=293/7	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: rs776902652; hg19: chr10-5945115;