rs1555788144
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006363.6(SEC23B):c.576_583delinsA(p.Lys193Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SEC23B
NM_006363.6 frameshift
NM_006363.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.93
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-18524642-CAAGGATT-A is Pathogenic according to our data. Variant chr20-18524642-CAAGGATT-A is described in ClinVar as [Pathogenic]. Clinvar id is 463383.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC23B | NM_006363.6 | c.576_583delinsA | p.Lys193Ter | frameshift_variant | 5/20 | ENST00000650089.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC23B | ENST00000650089.1 | c.576_583delinsA | p.Lys193Ter | frameshift_variant | 5/20 | NM_006363.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). This variant has not been reported in the literature in individuals with SEC23B-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys193*) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. - |
Congenital dyserythropoietic anemia, type II Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2017 | This sequence change creates a premature translational stop signal (p.Lys193*) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SEC23B-related disease. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at