rs77480566
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_205836.3(FBXO38):āc.87T>Cā(p.Tyr29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,599,796 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0025 ( 1 hom., cov: 32)
Exomes š: 0.0039 ( 15 hom. )
Consequence
FBXO38
NM_205836.3 synonymous
NM_205836.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0830
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 5-148394863-T-C is Benign according to our data. Variant chr5-148394863-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 473962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148394863-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.083 with no splicing effect.
BS2
?
High AC in GnomAd4 at 382 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBXO38 | NM_205836.3 | c.87T>C | p.Tyr29= | synonymous_variant | 2/22 | ENST00000340253.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXO38 | ENST00000340253.10 | c.87T>C | p.Tyr29= | synonymous_variant | 2/22 | 5 | NM_205836.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00251 AC: 382AN: 152170Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00285 AC: 681AN: 238650Hom.: 3 AF XY: 0.00275 AC XY: 356AN XY: 129314
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GnomAD4 exome AF: 0.00389 AC: 5626AN: 1447508Hom.: 15 Cov.: 30 AF XY: 0.00382 AC XY: 2748AN XY: 719892
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GnomAD4 genome ? AF: 0.00251 AC: 382AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.00218 AC XY: 162AN XY: 74462
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | FBXO38: BP4, BP7, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Distal hereditary motor neuropathy type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
FBXO38-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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