Variant summary: ATM c.9091C>T (p.Gln3031X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. There have not been any truncations downstream of this variant in our database that have been classified as pathogenic. The variant was absent in 251428 control chromosomes. c.9091C>T has been reported in the literature in an individual with a family history of breast cancer (Li_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.9091C>T (p.Gln3031Ter)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic/Likely pathogenic
5 out of 5 submissions contributed to this 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.
5
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000051.4(ATM):c.9091C>T (p.Gln3031Ter)
Variation ID: 920394 Accession: VCV000920394.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108365428 (GRCh38) [ NCBI UCSC ] 11: 108236155 (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 Jun 22, 2020 Feb 25, 2025 Mar 6, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000051.4:c.9091C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Gln3031Ter nonsense NM_001330368.2:c.640+20492G>A intron variant NM_001351110.2:c.694+20492G>A intron variant NM_001351834.2:c.9091C>T NP_001338763.1:p.Gln3031Ter nonsense NC_000011.10:g.108365428C>T NC_000011.9:g.108236155C>T NG_009830.1:g.147597C>T NG_054724.1:g.109405G>A LRG_135:g.147597C>T LRG_135t1:c.9091C>T LRG_135p1:p.Gln3031Ter - Protein change
- Q3031*
- Other names
- -
- Canonical SPDI
- NC_000011.10:108365427:C:T
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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
Help
The frequency of the allele represented by this VCV record.
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- 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. |
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| ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
11736 | 18941 | |
| C11orf65 | - | - | - |
GRCh38 GRCh37 |
9 | 7191 |
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 4, 2021 | RCV001179145.13 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 6, 2024 | RCV001247349.17 | |
| Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 6, 2024 | RCV001192363.10 |
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. |
Expand all rows
Collapse all rows
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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|---|---|---|---|---|---|
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Likely pathogenic
(Jun 17, 2019)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Familial cancer of breast |
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001360417.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
show
Variant summary: ATM c.9091C>T (p.Gln3031X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. There have not been any truncations downstream of this variant in our database that have been classified as pathogenic. The variant was absent in 251428 control chromosomes. c.9091C>T has been reported in the literature in an individual with a family history of breast cancer (Li_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
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|
Likely pathogenic
(Jan 15, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Color Diagnostics, LLC DBA Color Health
Accession: SCV001343753.2
First in ClinVar: Jun 22, 2020 Last updated: Jan 15, 2022 |
Comment:
show
This variant changes 1 nucleotide in exon 63 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Platform type: NGS
|
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Pathogenic
(Feb 06, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Familial cancer of breast |
Myriad Genetics, Inc.
Accession: SCV004930353.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
show
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
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Pathogenic
(Jan 04, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Ambry Genetics
Accession: SCV002682843.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
show
The p.Q3031* pathogenic mutation (also known as c.9091C>T), located in coding exon 62 of the ATM gene, results from a C to T substitution at nucleotide position 9091. This changes the amino acid from a glutamine to a stop codon within coding exon 62. This alteration occurs at the 3' terminus of theATM gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 26 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been reported in one breast cancer patient in China (Li JY et al. Int J Cancer. 2019 01;144:281-289). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Mar 06, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Ataxia-telangiectasia syndrome |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001420764.6
First in ClinVar: Jul 16, 2020 Last updated: Feb 25, 2025 |
Comment:
show
This sequence change creates a premature translational stop signal (p.Gln3031*) in the ATM gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the ATM protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 29752822). ClinVar contains an entry for this variant (Variation ID: 920394). This variant disrupts a region of the ATM protein in which other variant(s) (p.Arg3047*) have been determined to be pathogenic (PMID: 8755918, 10980530, 18560558, 19431188, 19691550, 26628246). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
Comment:
Comment:
This variant changes 1 nucleotide in exon 63 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Comment:
The p.Q3031* pathogenic mutation (also known as c.9091C>T), located in coding exon 62 of the ATM gene, results from a C to T substitution at nucleotide position 9091. This changes the amino acid from a glutamine to a stop codon within coding exon 62. This alteration occurs at the 3' terminus of theATM gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 26 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been reported in one breast cancer patient in China (Li JY et al. Int J Cancer. 2019 01;144:281-289). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
This sequence change creates a premature translational stop signal (p.Gln3031*) in the ATM gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the ATM protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 29752822). ClinVar contains an entry for this variant (Variation ID: 920394). This variant disrupts a region of the ATM protein in which other variant(s) (p.Arg3047*) have been determined to be pathogenic (PMID: 8755918, 10980530, 18560558, 19431188, 19691550, 26628246). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
| Novel ATM mutations with ataxia-telangiectasia. | Liu XL | Neuroscience letters | 2016 | PMID: 26628246 |
| Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families. | Chessa L | Annals of human genetics | 2009 | PMID: 19691550 |
| Modeling ATM mutant proteins from missense changes confirms retained kinase activity. | Barone G | Human mutation | 2009 | PMID: 19431188 |
| Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia. | Perfettini JL | PloS one | 2008 | PMID: 18560558 |
| Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia. | Laake K | Human mutation | 2000 | PMID: 10980530 |
| Mutations associated with variant phenotypes in ataxia-telangiectasia. | McConville CM | American journal of human genetics | 1996 | PMID: 8755918 |
Text-mined citations for rs2091249987 ...
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 15, 2025
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.