rs143782854

Variant names:

• chr10-5906211-C-A
• rs143782854
• NM_178150.3:c.332C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-5906211-C-A
• chr10-5906211-C-G
• chr10-5906211-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178150.3(FBH1):​c.332C>A​(p.Pro111Gln) 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 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. P111L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBH1 NM_178150.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05413434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBH1	NM_178150.3	c.332C>A	p.Pro111Gln	missense_variant	Exon 3 of 21	ENST00000362091.9	NP_835363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBH1	ENST00000362091.9	c.332C>A	p.Pro111Gln	missense_variant	Exon 3 of 21	1	NM_178150.3	ENSP00000355415.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.2
DANN	Benign	0.40
DEOGEN2	Benign	0.0063	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.030	.;N;N
REVEL	Benign	0.027
Sift	Benign	0.40	.;T;T
Sift4G	Benign	0.30	T;.;T
Polyphen		0.0010	.;B;B
Vest4		0.11
MutPred		0.12		.;Loss of glycosylation at P111 (P = 0.0104);.;
MVP		0.043
MPC		0.15
ClinPred		0.023	T
GERP RS		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.019
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143782854; hg19: chr10-5948174;