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
NM_205836.3 missense
Scores
4
7
6
Clinical Significance
Conservation
PhyloP100: 5.50
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 |
---|---|---|---|---|---|---|---|
FBXO38 | NM_205836.3 | c.2903C>G | p.Pro968Arg | missense_variant | 18/22 | ENST00000340253.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXO38 | ENST00000340253.10 | c.2903C>G | p.Pro968Arg | missense_variant | 18/22 | 5 | NM_205836.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152062Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251174Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135740
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GnomAD4 exome AF: 0.0000862 AC: 126AN: 1461632Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58AN XY: 727118
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74276
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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 submitter | clinical testing | Invitae | Apr 10, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Benign
T;D;D;T
Sift4G
Benign
T;T;T;T
Polyphen
P;D;D;P
Vest4
MVP
MPC
1.0
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at