chr16-87335300-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_024735.5(FBXO31):c.996+4A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000026 in 1,613,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 2 hom. )
Consequence
FBXO31
NM_024735.5 splice_donor_region, intron
NM_024735.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.8509
2
Clinical Significance
Conservation
PhyloP100: 4.19
Genes affected
FBXO31 (HGNC:16510): (F-box protein 31) This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBXO31 | NM_024735.5 | c.996+4A>G | splice_donor_region_variant, intron_variant | ENST00000311635.12 | |||
FBXO31 | NM_001282683.2 | c.480+4A>G | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXO31 | ENST00000311635.12 | c.996+4A>G | splice_donor_region_variant, intron_variant | 1 | NM_024735.5 | P1 | |||
FBXO31 | ENST00000618298.6 | c.480+4A>G | splice_donor_region_variant, intron_variant | 5 | |||||
FBXO31 | ENST00000636077.2 | c.1083+4A>G | splice_donor_region_variant, intron_variant | 5 | |||||
FBXO31 | ENST00000565593.1 | c.288-1179A>G | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152166Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250162Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135368
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460952Hom.: 2 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 726786
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal recessive 45 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 24, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at