NM_178150.3:c.52G>C

Variant names:

• chr10-5903070-G-C
• NM_178150.3:c.52G>C

Variant summary

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

The NM_178150.3(FBH1):​c.52G>C​(p.Ala18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBH1 NM_178150.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.725
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.52G>C	p.Ala18Pro	missense	Exon 2 of 21	NP_835363.1	Q8NFZ0-1
	FBH1	NM_032807.5		c.205G>C	p.Ala69Pro	missense	Exon 3 of 22	NP_116196.3
	FBH1	NM_001258452.2		c.-171G>C		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.52G>C	p.Ala18Pro	missense	Exon 2 of 21	ENSP00000355415.4	Q8NFZ0-1
	FBH1	ENST00000379999.6	TSL:1	c.205G>C	p.Ala69Pro	missense	Exon 3 of 22	ENSP00000369335.5	Q8NFZ0-2
	FBH1	ENST00000908866.1		c.52G>C	p.Ala18Pro	missense	Exon 2 of 22	ENSP00000578925.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	0.0047	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.0063
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.85	T
PhyloP100		0.72
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.12
Sift	Benign	0.032	D
Sift4G	Uncertain	0.041	D
Polyphen		0.90	P
Vest4		0.53
MutPred		0.54		Loss of helix (P = 0.0068)
MVP		0.21
MPC		0.58
ClinPred		0.55	D
GERP RS		3.4
Varity_R		0.23
gMVP		0.56
Mutation Taster		=71/29	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

hg19: chr10-5945033;