chr9-89319800-A-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024077.5(SECISBP2):c.182+3A>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SECISBP2
NM_024077.5 splice_donor_region, intron
NM_024077.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 3.53
Genes affected
SECISBP2 (HGNC:30972): (SECIS binding protein 2) The protein encoded by this gene is one of the essential components of the machinery involved in co-translational insertion of selenocysteine (Sec) into selenoproteins. Sec is encoded by the UGA codon, which normally signals translation termination. The recoding of UGA as Sec codon requires a Sec insertion sequence (SECIS) element; present in the 3' untranslated regions of eukaryotic selenoprotein mRNAs. This protein specifically binds to the SECIS element, which is stimulated by a Sec-specific translation elongation factor. Mutations in this gene have been associated with reduction in enzymatic activity of type II iodothyronine deiodinase (a selenoprotein) and abnormal thyroid hormone metabolism. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SECISBP2 | NM_024077.5 | c.182+3A>T | splice_donor_region_variant, intron_variant | ENST00000375807.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SECISBP2 | ENST00000375807.8 | c.182+3A>T | splice_donor_region_variant, intron_variant | 1 | NM_024077.5 | P2 | |||
SECISBP2 | ENST00000339901.8 | c.84+3A>T | splice_donor_region_variant, intron_variant | 1 | A2 | ||||
SECISBP2 | ENST00000534113.6 | c.-23+3A>T | splice_donor_region_variant, intron_variant | 2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SECISBP2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 12, 2022 | The SECISBP2 c.182+3A>T variant is predicted to interfere with splicing. This variant is predicted to interfere with splicing at the consensus donor site based on splicing prediction programs (Alamut Visual Plus v.1.6.1). However, these prediction programs are inequivalent to functional data. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.