Variant 17-38951613-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001008777.3(FBXO47):c.584G>A(p.Arg195His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

FBXO47
NM_001008777.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

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

FBXO47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3304438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FBXO47	NM_001008777.3 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	6/11	ENST00000378079.3	NP_001008777.2
FBXO47	XM_011524865.3 linkuse as main transcript	c.506G>A	p.Arg169His	missense_variant	6/11		XP_011523167.1
FBXO47	XM_011524866.4 linkuse as main transcript	c.413G>A	p.Arg138His	missense_variant	5/10		XP_011523168.1
FBXO47	XM_011524867.3 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	6/10		XP_011523169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO47	ENST00000378079.3 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	6/11	1	NM_001008777.3	ENSP00000367319	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251272

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461444

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.584G>A (p.R195H) alteration is located in exon 6 (coding exon 5) of the FBXO47 gene. This alteration results from a G to A substitution at nucleotide position 584, causing the arginine (R) at amino acid position 195 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.0080

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

M_CAP

Benign

0.027

MetaRNN

Benign

0.33

MetaSVM

Uncertain

0.068

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.41

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.32

MutPred

0.35

Gain of ubiquitination at K196 (P = 0.0498);

MVP

0.73

MPC

0.089

ClinPred

0.43

GERP RS

5.5

Varity_R

0.25

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over