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GeneBe

rs141168806

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP6_ModerateBS2

The NM_205836.3(FBXO38):c.2903C>G(p.Pro968Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000093 in 1,613,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P968P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

FBXO38
NM_205836.3 missense

Scores

4
7
6

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.50
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
Missense variant where missense usually causes diseases, FBXO38
BP6
Variant 5-148438377-C-G is Benign according to our data. Variant chr5-148438377-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 541005.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FBXO38NM_205836.3 linkuse as main transcriptc.2903C>G p.Pro968Arg missense_variant 18/22 ENST00000340253.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FBXO38ENST00000340253.10 linkuse as main transcriptc.2903C>G p.Pro968Arg missense_variant 18/225 NM_205836.3 P3Q6PIJ6-1

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152062
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000721
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251174
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135740
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000289
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:
0.0000793
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000862
AC:
126
AN:
1461632
Hom.:
0
Cov.:
31
AF XY:
0.0000798
AC XY:
58
AN XY:
727118
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000268
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:
0.0000971
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152062
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000721
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000893
Hom.:
0
Bravo
AF:
0.000125
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Distal hereditary motor neuropathy type 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeApr 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Uncertain
0.050
Cadd
Pathogenic
27
Dann
Uncertain
1.0
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D;D;.
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.70
D;D;D;D
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.7
D;D;D;D
REVEL
Uncertain
0.30
Sift
Benign
0.12
T;D;D;T
Sift4G
Benign
0.097
T;T;T;T
Polyphen
0.83
P;D;D;P
Vest4
0.93
MVP
0.27
MPC
1.0
ClinPred
0.36
T
GERP RS
5.9
Varity_R
0.52
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs141168806; hg19: chr5-147817940; API