rs121918225
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_006363.6(SEC23B):c.970C>T(p.Arg324Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,952 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
Consequence
NM_006363.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC23B | NM_006363.6 | c.970C>T | p.Arg324Ter | stop_gained | 8/20 | ENST00000650089.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC23B | ENST00000650089.1 | c.970C>T | p.Arg324Ter | stop_gained | 8/20 | NM_006363.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152084Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251340Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135842
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727238
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152084Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74280
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 09, 2023 | The SEC23B c.970C>T; p.Arg324Ter variant (rs121918225) is reported in the literature as a compound heterozygous variant in an individual affected with congenital dyserythropoietic anemia type II (Schwarz 2009). This variant is also reported in ClinVar (Variation ID: 1226). This variant is found predominantly in the non-Finnish European population with an allele frequency of 0.009% (12/129050 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Schwarz K et al. Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nature genetics. 2009 Aug. PMID: 19561605 - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 29, 2022 | - - |
Congenital dyserythropoietic anemia, type II Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2009 | - - |
Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 16, 2023 | This sequence change creates a premature translational stop signal (p.Arg324*) 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). This variant is present in population databases (rs121918225, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with congenital dyserythropoietic anemia type 2 (PMID: 19561605). ClinVar contains an entry for this variant (Variation ID: 1226). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at