NM_001008777.3:c.460G>A

Variant names:

• chr17-38954903-C-T
• NM_001008777.3:c.460G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008777.3(FBXO47):​c.460G>A​(p.Ala154Thr) 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. 16/21 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: FBXO47 NM_001008777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.245

Genes affected

FBXO47 (HGNC:31969): (F-box protein 47)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08274269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO47	NM_001008777.3	c.460G>A	p.Ala154Thr	missense_variant	Exon 5 of 11	ENST00000378079.3	NP_001008777.2
FBXO47	XM_011524865.3	c.382G>A	p.Ala128Thr	missense_variant	Exon 5 of 11		XP_011523167.1
FBXO47	XM_011524866.4	c.289G>A	p.Ala97Thr	missense_variant	Exon 4 of 10		XP_011523168.1
FBXO47	XM_011524867.3	c.460G>A	p.Ala154Thr	missense_variant	Exon 5 of 10		XP_011523169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO47	ENST00000378079.3	c.460G>A	p.Ala154Thr	missense_variant	Exon 5 of 11	1	NM_001008777.3	ENSP00000367319.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.460G>A (p.A154T) alteration is located in exon 5 (coding exon 4) of the FBXO47 gene. This alteration results from a G to A substitution at nucleotide position 460, causing the alanine (A) at amino acid position 154 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.048
Sift	Benign	0.26	T
Sift4G	Benign	0.63	T
Polyphen		0.085	B
Vest4		0.065
MutPred		0.35		Gain of relative solvent accessibility (P = 0.09);
MVP		0.49
MPC		0.067
ClinPred		0.062	T
GERP RS		3.7
Varity_R		0.042
gMVP		0.070

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: chr17-37111156;