For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of spherocytosis (PMID: 29572776). This variant is present in population databases (rs150471537, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Arg1306*) in the SPTB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPTB are known to be pathogenic (PMID: 8844207, 26830532, 27292444).
ClinVar Genomic variation as it relates to human health
NM_001355436.2(SPTB):c.3916C>T (p.Arg1306Ter)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(7)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
7
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001355436.2(SPTB):c.3916C>T (p.Arg1306Ter)
Variation ID: 544816 Accession: VCV000544816.27
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q23.3 14: 64784333 (GRCh38) [ NCBI UCSC ] 14: 65251051 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 28, 2018 Oct 26, 2024 Aug 29, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001355436.2:c.3916C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001342365.1:p.Arg1306Ter nonsense NM_001024858.4:c.3916C>T NP_001020029.1:p.Arg1306Ter nonsense NM_001355437.2:c.3916C>T NP_001342366.1:p.Arg1306Ter nonsense NC_000014.9:g.64784333G>A NC_000014.8:g.65251051G>A NG_016202.2:g.100560C>T LRG_1130:g.100560C>T LRG_1130t1:c.3916C>T LRG_1130p1:p.Arg1306Ter LRG_1130t2:c.3916C>T LRG_1130p2:p.Arg1306Ter - Protein change
- R1306*
- Other names
- -
- Canonical SPDI
- NC_000014.9:64784332:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| SPTB | - | - |
GRCh38 GRCh37 |
1023 | 1055 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 30, 2023 | RCV000655913.4 | |
| Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Aug 29, 2023 | RCV001507847.26 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Feb 27, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary spherocytosis type 2
Affected status: yes
Allele origin:
germline
|
Department of Genetic, Henri Mondor Hospital, Assistance Publique des Hôpitaux de Paris
Accession: SCV000777862.1
First in ClinVar: May 28, 2018 Last updated: May 28, 2018 |
|
|
|
Pathogenic
(Jun 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV004238371.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(May 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002118537.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of spherocytosis (PMID: 29572776). This … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of spherocytosis (PMID: 29572776). This variant is present in population databases (rs150471537, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Arg1306*) in the SPTB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPTB are known to be pathogenic (PMID: 8844207, 26830532, 27292444). (less)
|
|
|
Pathogenic
(Aug 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004562430.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The SPTB c.3916C>T; p.Arg1306Ter variant (rs150471537) is reported in the literature in two individuals affected with hereditary spherocytosis (Mansour-Hendili 2020, Wang 2018). This variant is … (more)
The SPTB c.3916C>T; p.Arg1306Ter variant (rs150471537) is reported in the literature in two individuals affected with hereditary spherocytosis (Mansour-Hendili 2020, Wang 2018). This variant is also reported in ClinVar (Variation ID: 544816). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. 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 Mansour-Hendili L et al. Exome sequencing for diagnosis of congenital hemolytic anemia. Orphanet J Rare Dis. 2020 Jul 8. PMID: 32641076 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776 (less)
|
|
|
Likely pathogenic
(Aug 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713666.2
First in ClinVar: Jun 15, 2021 Last updated: Jun 02, 2024 |
Comment:
PVS1, PM2
Number of individuals with the variant: 6
|
|
|
Pathogenic
(Jun 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010296.12
First in ClinVar: Jul 16, 2023 Last updated: Oct 20, 2024 |
Comment:
SPTB: PVS1, PS4:Moderate, PM2:Supporting, PM6:Supporting
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jan 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary spherocytosis type 2
Affected status: yes
Allele origin:
germline
|
Institute of Immunology and Genetics Kaiserslautern
Accession: SCV005382162.1
First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024 |
Comment:
ACMG Criteria: PVS1, PM2, PP5; Variant was found in heterozygous state.
Clinical Features:
Spherocytosis (present)
|
Comment:
Comment:
The SPTB c.3916C>T; p.Arg1306Ter variant (rs150471537) is reported in the literature in two individuals affected with hereditary spherocytosis (Mansour-Hendili 2020, Wang 2018). This variant is also reported in ClinVar (Variation ID: 544816). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. 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 Mansour-Hendili L et al. Exome sequencing for diagnosis of congenital hemolytic anemia. Orphanet J Rare Dis. 2020 Jul 8. PMID: 32641076 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776
Comment:
PVS1, PM2
Comment:
SPTB: PVS1, PS4:Moderate, PM2:Supporting, PM6:Supporting
Comment:
ACMG Criteria: PVS1, PM2, PP5; Variant was found in heterozygous state.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of spherocytosis (PMID: 29572776). This variant is present in population databases (rs150471537, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Arg1306*) in the SPTB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPTB are known to be pathogenic (PMID: 8844207, 26830532, 27292444).
Comment:
The SPTB c.3916C>T; p.Arg1306Ter variant (rs150471537) is reported in the literature in two individuals affected with hereditary spherocytosis (Mansour-Hendili 2020, Wang 2018). This variant is also reported in ClinVar (Variation ID: 544816). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. 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 Mansour-Hendili L et al. Exome sequencing for diagnosis of congenital hemolytic anemia. Orphanet J Rare Dis. 2020 Jul 8. PMID: 32641076 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776
Comment:
PVS1, PM2
Comment:
SPTB: PVS1, PS4:Moderate, PM2:Supporting, PM6:Supporting
Comment:
ACMG Criteria: PVS1, PM2, PP5; Variant was found in heterozygous state.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. | Wang R | Science China. Life sciences | 2018 | PMID: 29572776 |
| Clinical utility of next-generation sequencing in the diagnosis of hereditary haemolytic anaemias. | Agarwal AM | British journal of haematology | 2016 | PMID: 27292444 |
| Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis. | Park J | Clinical genetics | 2016 | PMID: 26830532 |
| Spectrin mutations in hereditary elliptocytosis and hereditary spherocytosis. | Maillet P | Human mutation | 1996 | PMID: 8844207 |
Text-mined citations for rs150471537 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 03, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.