ClinVar Genomic variation as it relates to human health
NM_024642.5(GALNT12):c.907G>A (p.Asp303Asn)
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.
Uncertain significance(2); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_024642.5(GALNT12):c.907G>A (p.Asp303Asn)
Variation ID: 224569 Accession: VCV000224569.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q22.33 9: 98831947 (GRCh38) [ NCBI UCSC ] 9: 101594229 (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 Mar 20, 2016 May 1, 2024 Jan 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024642.5:c.907G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_078918.3:p.Asp303Asn missense NC_000009.12:g.98831947G>A NC_000009.11:g.101594229G>A NG_028218.1:g.29249G>A Q8IXK2:p.Asp303Asn - Protein change
- D303N
- Other names
- -
- Canonical SPDI
- NC_000009.12:98831946:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- polypeptide_partial_loss_of_function Sequence Ontology [SO:0001561]
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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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0.00080 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00080
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00092
1000 Genomes Project 30x 0.00094
Exome Aggregation Consortium (ExAC) 0.00123
The Genome Aggregation Database (gnomAD), exomes 0.00124
The Genome Aggregation Database (gnomAD) 0.00129
Trans-Omics for Precision Medicine (TOPMed) 0.00132
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 | ||
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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
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. |
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GALNT12 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1313 | 1420 |
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. |
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Uncertain significance (1) |
criteria provided, conflicting classifications
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Nov 20, 2015 | RCV000210098.16 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 28, 2024 | RCV000229689.20 | |
Benign (1) |
no assertion criteria provided
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- | RCV000656380.8 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 14, 2020 | RCV003937792.1 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 23, 2020 | RCV004020573.1 |
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. |
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Uncertain significance
(Nov 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown, yes
Allele origin:
germline
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University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266172.1
First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
colon cancer (present) , breast cancer (present)
Age: 30-39 years
Comment on evidence:
two primary breast cancers were observed
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 40-49 years
Comment on evidence:
three primary breast cancers were observed
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
bilateral breast cancer (present) , skin cancer (present)
Age: 30-39 years
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 40-49 years
Comment on evidence:
two primary breast cancers were observed
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Uncertain significance
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010985.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Likely benign
(Oct 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002047046.3
First in ClinVar: Jan 03, 2022 Last updated: Jan 06, 2024 |
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Likely benign
(Jan 28, 2024)
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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: SCV000290792.9
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
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Likely benign
(Jul 14, 2020)
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criteria provided, single submitter
Method: clinical testing
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GALNT12-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004747886.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Mar 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000673501.5
First in ClinVar: Mar 20, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(-)
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no assertion criteria provided
Method: research
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Adenomatous polyposis coli, attenuated
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Molecular Oncology Laboratory, Hospital Clínico San Carlos
Accession: SCV000579211.1
First in ClinVar: Jun 12, 2018 Last updated: Jun 12, 2018 |
Comment:
No statistical differences in allelic frequencies between polyposis subjects and controls. No aberrant glycosylation patterns detected in adenomas of polyposis cases.
Number of individuals with the variant: 4
Clinical Features:
Adenomatous colonic polyposis (present)
Geographic origin: Spain
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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polypeptide_partial_loss_of_function
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Molecular Oncology Laboratory, Hospital Clínico San Carlos
Accession: SCV000579211.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients. | Djursby M | Frontiers in genetics | 2020 | PMID: 33193653 |
The structure of the colorectal cancer-associated enzyme GalNAc-T12 reveals how nonconserved residues dictate its function. | Fernandez AJ | Proceedings of the National Academy of Sciences of the United States of America | 2019 | PMID: 31548401 |
Evidence for GALNT12 as a moderate penetrance gene for colorectal cancer. | Evans DR | Human mutation | 2018 | PMID: 29749045 |
Assessment of Tumor Sequencing as a Replacement for Lynch Syndrome Screening and Current Molecular Tests for Patients With Colorectal Cancer. | Hampel H | JAMA oncology | 2018 | PMID: 29596542 |
Role of GALNT12 in the genetic predisposition to attenuated adenomatous polyposis syndrome. | Lorca V | PloS one | 2017 | PMID: 29095867 |
Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes. | DeRycke MS | Molecular genetics & genomic medicine | 2017 | PMID: 28944238 |
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Improving performance of multigene panels for genomic analysis of cancer predisposition. | Shirts BH | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26845104 |
Large numbers of individuals are required to classify and define risk for rare variants in known cancer risk genes. | Shirts BH | Genetics in medicine : official journal of the American College of Medical Genetics | 2014 | PMID: 24357849 |
Clinically significant missense variants in human GALNT3, GALNT8, GALNT12, and GALNT13 genes: intriguing in silico findings. | Hussain MRM | Journal of cellular biochemistry | 2014 | PMID: 24038392 |
Inherited deleterious variants in GALNT12 are associated with CRC susceptibility. | Clarke E | Human mutation | 2012 | PMID: 22461326 |
Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22. | Gray-McGuire C | Cancer research | 2010 | PMID: 20551049 |
Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. | Guda K | Proceedings of the National Academy of Sciences of the United States of America | 2009 | PMID: 19617566 |
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Text-mined citations for rs145236923 ...
HelpRecord last updated May 01, 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.