rs10043775

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_205836.3(FBXO38):c.1774T>C(p.Ser592Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,612,442 control chromosomes in the GnomAD database, including 58,593 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S592A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.27 ( 5608 hom., cov: 32)

Exomes 𝑓: 0.27 ( 52985 hom. )

Consequence

FBXO38
NM_205836.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.44

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025879145).

BP6

Variant 5-148425557-T-C is Benign according to our data. Variant chr5-148425557-T-C is described in ClinVar as [Benign]. Clinvar id is 1169150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148425557-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO38	NM_205836.3 link	c.1774T>C	p.Ser592Pro	missense_variant	Exon 14 of 22	ENST00000340253.10	NP_995308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO38	ENST00000340253.10 link	c.1774T>C	p.Ser592Pro	missense_variant	Exon 14 of 22	5	NM_205836.3	ENSP00000342023.6		Q6PIJ6-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41055

AN:

151776

Hom.:

5597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.268

AC:

67370

AN:

251128

Hom.:

9182

AF XY:

0.269

AC XY:

36539

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.267

AC:

390551

AN:

1460546

Hom.:

52985

Cov.:

AF XY:

0.268

AC XY:

194653

AN XY:

726636

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.271

AC:

41097

AN:

151896

Hom.:

5608

Cov.:

AF XY:

0.267

AC XY:

19845

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.267

Hom.:

10244

Bravo

AF:

0.272

TwinsUK

AF:

0.274

AC:

1015

ALSPAC

AF:

0.267

AC:

1029

ESP6500AA

AF:

0.291

AC:

1284

ESP6500EA

AF:

0.264

AC:

2267

ExAC

AF:

0.269

AC:

32647

Asia WGS

AF:

0.259

AC:

901

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.268

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Distal hereditary motor neuropathy type 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neuronopathy, distal hereditary motor, type 2D

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.012

.;T;.;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.18

T;T;T;.

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

2.1

N;N;N;N

REVEL

Benign

0.096

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.89

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.10

MPC

0.14

ClinPred

0.0025

GERP RS

4.9

Varity_R

0.10

gMVP

0.096

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