20-18525888-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_006363.6(SEC23B):c.790C>T(p.Arg264*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
SEC23B
NM_006363.6 stop_gained
NM_006363.6 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 2.61
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 16 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 20-18525888-C-T is Pathogenic according to our data. Variant chr20-18525888-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEC23B | NM_006363.6 | c.790C>T | p.Arg264* | stop_gained | 7/20 | ENST00000650089.1 | NP_006354.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEC23B | ENST00000650089.1 | c.790C>T | p.Arg264* | stop_gained | 7/20 | NM_006363.6 | ENSP00000497473.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251440Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727242
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74336
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 08, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1225). This premature translational stop signal has been observed in individual(s) with dyserythropoietic anemia (PMID: 19561605). This variant is present in population databases (rs121918224, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg264*) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2018 | - - |
Congenital dyserythropoietic anemia, type II Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2009 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
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