Variant rs11949133 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_205836.3(FBXO38):c.2680G>A(p.Ala894Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,613,296 control chromosomes in the GnomAD database, including 422 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 224 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 198 hom. )

Consequence

FBXO38
NM_205836.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

FBXO38 (HGNC:28844): (F-box protein 38) This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

FBXO38 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), FBXO38. . Gene score misZ 2.8126 (greater than the threshold 3.09). Trascript score misZ 3.83 (greater than threshold 3.09). GenCC has associacion of gene with distal hereditary motor neuropathy type 2, neuronopathy, distal hereditary motor, type 2D, distal hereditary motor neuropathy.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015137196).

BP6

Variant 5-148433450-G-A is Benign according to our data. Variant chr5-148433450-G-A is described in ClinVar as [Benign]. Clinvar id is 473956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148433450-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO38	NM_205836.3 linkuse as main transcript	c.2680G>A	p.Ala894Thr	missense_variant	16/22	ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10 linkuse as main transcript	c.2680G>A	p.Ala894Thr	missense_variant	16/22	5	NM_205836.3	ENSP00000342023	P3	Q6PIJ6-1

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

4557

AN:

152016

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.00801

AC:

2007

AN:

250688

Hom.:

AF XY:

0.00567

AC XY:

768

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.00654

GnomAD4 exome

AF:

0.00319

AC:

4664

AN:

1461162

Hom.:

198

Cov.:

AF XY:

0.00279

AC XY:

2031

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.00811

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000432

Gnomad4 OTH exome

AF:

0.00701

GnomAD4 genome

AF:

0.0301

AC:

4578

AN:

152134

Hom.:

224

Cov.:

AF XY:

0.0286

AC XY:

2125

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.00895

Hom.:

Bravo

AF:

0.0329

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0965

AC:

425

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00957

AC:

1162

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Distal hereditary motor neuropathy type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

.;T;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;D;D;.

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;.;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.32

N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.014

B;B;B;B

Vest4

0.12

MVP

0.17

MPC

1.8

ClinPred

0.024

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.28

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