rs371786580
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_006363.6(SEC23B):c.1665+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,614,028 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00043 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 2 hom. )
Consequence
SEC23B
NM_006363.6 splice_donor_region, intron
NM_006363.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.002276
2
Clinical Significance
Conservation
PhyloP100: 0.0700
Genes affected
SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC23B | NM_006363.6 | c.1665+6T>C | splice_donor_region_variant, intron_variant | ENST00000650089.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC23B | ENST00000650089.1 | c.1665+6T>C | splice_donor_region_variant, intron_variant | NM_006363.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 152150Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000450 AC: 113AN: 251368Hom.: 0 AF XY: 0.000427 AC XY: 58AN XY: 135882
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GnomAD4 exome AF: 0.000653 AC: 954AN: 1461878Hom.: 2 Cov.: 32 AF XY: 0.000645 AC XY: 469AN XY: 727240
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 12, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 02, 2021 | - - |
Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2022 | This sequence change falls in intron 14 of the SEC23B gene. It does not directly change the encoded amino acid sequence of the SEC23B protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs371786580, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SEC23B-related conditions. ClinVar contains an entry for this variant (Variation ID: 571371). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Congenital dyserythropoietic anemia, type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
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
DS_DL_spliceai
Position offset: -6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at