Variant 17-38954914-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001008777.3(FBXO47):c.449A>G(p.Asn150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FBXO47
NM_001008777.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025633812).

BP6

Variant 17-38954914-T-C is Benign according to our data. Variant chr17-38954914-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3093786.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FBXO47	NM_001008777.3 linkuse as main transcript	c.449A>G	p.Asn150Ser	missense_variant	5/11	ENST00000378079.3	NP_001008777.2
FBXO47	XM_011524865.3 linkuse as main transcript	c.371A>G	p.Asn124Ser	missense_variant	5/11		XP_011523167.1
FBXO47	XM_011524866.4 linkuse as main transcript	c.278A>G	p.Asn93Ser	missense_variant	4/10		XP_011523168.1
FBXO47	XM_011524867.3 linkuse as main transcript	c.449A>G	p.Asn150Ser	missense_variant	5/10		XP_011523169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO47	ENST00000378079.3 linkuse as main transcript	c.449A>G	p.Asn150Ser	missense_variant	5/11	1	NM_001008777.3	ENSP00000367319	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248420

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.4

DANN

Benign

0.57

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.64

M_CAP

Benign

0.010

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.28

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.80

REVEL

Benign

0.17

Sift

Benign

0.83

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.099

MutPred

0.43

Loss of solvent accessibility (P = 0.0058);

MVP

0.048

MPC

0.057

ClinPred

0.022

GERP RS

-4.4

Varity_R

0.041

gMVP

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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