chr1-11658368-A-G

Position:

• chr1-11658368-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033182.7(FBXO44):​c.367A>G​(p.Lys123Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXO44 NM_033182.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

Genes affected

FBXO44 (HGNC:24847): (F-box protein 44) 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. It is also a member of the NFB42 (neural F Box 42 kDa) family, similar to F-box only protein 2 and F-box only protein 6. Several alternatively spliced transcript variants encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

FBXO44 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40920278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO44	NM_033182.7	c.367A>G	p.Lys123Glu	missense_variant	3/6	ENST00000251547.10	NP_149438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO44	ENST00000251547.10	c.367A>G	p.Lys123Glu	missense_variant	3/6	1	NM_033182.7	ENSP00000251547.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.367A>G (p.K123E) alteration is located in exon 4 (coding exon 2) of the FBXO44 gene. This alteration results from a A to G substitution at nucleotide position 367, causing the lysine (K) at amino acid position 123 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.35	T;T
Polyphen		0.84	P;P
Vest4		0.40
MutPred		0.59		Loss of methylation at K123 (P = 0.0011);Loss of methylation at K123 (P = 0.0011);
MVP		0.42
MPC		0.85
ClinPred		0.91	D
GERP RS		5.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-11718425;