17-38938587-T-C

Position:

• chr17-38938587-T-C

Variant summary

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

The NM_001008777.3(FBXO47):​c.1229A>G​(p.Gln410Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,304 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FBXO47 NM_001008777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO47	NM_001008777.3	c.1229A>G	p.Gln410Arg	missense_variant	10/11	ENST00000378079.3	NP_001008777.2
FBXO47	XM_011524865.3	c.1151A>G	p.Gln384Arg	missense_variant	10/11		XP_011523167.1
FBXO47	XM_011524866.4	c.1058A>G	p.Gln353Arg	missense_variant	9/10		XP_011523168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO47	ENST00000378079.3	c.1229A>G	p.Gln410Arg	missense_variant	10/11	1	NM_001008777.3	ENSP00000367319	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 251040 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459304 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

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

Apr 12, 2022

The c.1229A>G (p.Q410R) alteration is located in exon 10 (coding exon 9) of the FBXO47 gene. This alteration results from a A to G substitution at nucleotide position 1229, causing the glutamine (Q) at amino acid position 410 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.57
MutPred		0.38		Gain of solvent accessibility (P = 0.0584);
MVP		0.81
MPC		0.27
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs1254021375; hg19: chr17-37094840; COSMIC: COSV65241728;