ClinVar Genomic variation as it relates to human health
NM_000545.8(HNF1A):c.160C>T (p.Arg54Ter)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000545.8(HNF1A):c.160C>T (p.Arg54Ter)
Variation ID: 805632 Accession: VCV000805632.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.31 12: 120978928 (GRCh38) [ NCBI UCSC ] 12: 121416731 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jan 19, 2020 Feb 14, 2024 Dec 28, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000545.8:c.160C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000536.6:p.Arg54Ter nonsense NM_001306179.2:c.160C>T NP_001293108.2:p.Arg54Ter nonsense NC_000012.12:g.120978928C>T NC_000012.11:g.121416731C>T NG_011731.2:g.5183C>T LRG_522:g.5183C>T LRG_522t1:c.160C>T - Protein change
- R54*
- Other names
- NM_000545.8(HNF1A):c.160C>T
- p.Arg54Ter
- Canonical SPDI
- NC_000012.12:120978927:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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HNF1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
865 | 954 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 22, 2021 | RCV000993267.5 | |
Pathogenic (1) |
reviewed by expert panel
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Dec 28, 2021 | RCV001810489.3 |
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
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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
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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. |
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Pathogenic
(Dec 28, 2021)
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reviewed by expert panel
Method: curation
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Monogenic diabetes
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Monogenic Diabetes Variant Curation Expert Panel
Accession: SCV002059998.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
The c.160C>T variant in the HNF1 homeobox A gene, HNF1A, results in a premature termination at codon 54 (p.(Arg54Ter)) of NM_000545.8. This variant, located in … (more)
The c.160C>T variant in the HNF1 homeobox A gene, HNF1A, results in a premature termination at codon 54 (p.(Arg54Ter)) of NM_000545.8. This variant, located in biologically relevant exon 1/10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent in gnomAD v2.1.1. (PM2_Supporting). This variant was identified in 11 unrelated individuals with non-autoimmune/insulin-dependent diabetes (PS4; PMID:21224407, PMID:24905847, PMID:25414397, PMID:26050565, ClinVar ID 805632, internal lab contributors). This variant was identified in an individual with a clinical picture highly specific for HNF1A-MODY (MODY probability calculator >50%, negative genetic testing for HNF4A, and sensitive to sulfonylureas) (PP4_Moderate, internal lab contributor). This variant was identified as a de novo occurrence with confirmed parental relationships in an individual with non-autoimmune diabetes, but whose clinical picture is not highly specific for HNF1A-MODY (PS2_Moderate; internal lab contributor). This variant segregates with diabetes with 9 informative meioses in 5 families with diabetes (PP1_Strong; PMID:26050565, internal lab contributors). Taken together, this evidence supports the classification of this variant as pathogenic for HNF1A-MODY by the ClinGen MDEP (PVS1, PM2_Supporting, PS4, PP4_Moderate, PP1_Strong, PS2_Moderate). (less)
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Pathogenic
(Jan 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics Inc
Accession: SCV001146103.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
Comment:
The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one … (more)
The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. (less)
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Pathogenic
(Aug 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002146276.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg54*) in the HNF1A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg54*) in the HNF1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HNF1A are known to be pathogenic (PMID: 15928245, 18003757). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 12547858, 25414397). ClinVar contains an entry for this variant (Variation ID: 805632). For these reasons, this variant has been classified as Pathogenic. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Not quite type 1 or type 2, what now? Review of monogenic, mitochondrial, and syndromic diabetes. | Yeung RO | Reviews in endocrine & metabolic disorders | 2018 | PMID: 29777474 |
Low prevalence of HNF1A mutations after molecular screening of multiple MODY genes in 58 Italian families recruited in the pediatric or adult diabetes clinic from a single Italian hospital. | Delvecchio M | Diabetes care | 2014 | PMID: 25414397 |
Genetic and clinical characteristics of patients with HNF1A gene variations from the German-Austrian DPV database. | Awa WL | European journal of endocrinology | 2011 | PMID: 21224407 |
The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3. | Bellanné-Chantelot C | Diabetes | 2008 | PMID: 18003757 |
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. | Ellard S | Human mutation | 2006 | PMID: 16917892 |
Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1. | Johansen A | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 15928245 |
Identifying hepatic nuclear factor 1alpha mutations in children and young adults with a clinical diagnosis of type 1 diabetes. | Lambert AP | Diabetes care | 2003 | PMID: 12547858 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/b134b21e-7bec-494b-b2e1-866ae6cc7eab | - | - | - | - |
Text-mined citations for rs766956862 ...
HelpRecord last updated Feb 14, 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.