rs121918226
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_006363.6(SEC23B):c.649C>T(p.Arg217Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,613,850 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006363.6 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.649C>T | p.Arg217Ter | stop_gained | 6/20 | ENST00000650089.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC23B | ENST00000650089.1 | c.649C>T | p.Arg217Ter | stop_gained | 6/20 | NM_006363.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 151964Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251350Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135836
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461886Hom.: 0 Cov.: 35 AF XY: 0.0000591 AC XY: 43AN XY: 727240
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 151964Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74210
ClinVar
Submissions by phenotype
Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 23, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | This sequence change creates a premature translational stop signal (p.Arg217*) 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 (rs121918226, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with congenital dyserythropoietic anemia (PMID: 19561605). ClinVar contains an entry for this variant (Variation ID: 1227). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 06, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 30, 2014 | - - |
Congenital dyserythropoietic anemia, type II Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2009 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Jun 13, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at