VCV000546687.46 - ClinVar

NM_000051.4(ATM):c.3567del (p.Leu1189_Val1190insTer)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)

3 out of 3 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000051.4(ATM):c.3567del (p.Leu1189_Val1190insTer)

Variation ID: 546687 Accession: VCV000546687.46

Type and length

Deletion, 1 bp

Location

Cytogenetic: 11q22.3 11: 108281158 (GRCh38) [ NCBI UCSC ] 11: 108151885 (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	Jul 9, 2018	Apr 25, 2026	Jan 13, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000051.4:c.3567del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000042.3:p.Leu1189_Val1190insTer	frameshift
NM_000051.3:c.3567delT
NM_001351834.2:c.3567del	NP_001338763.1:p.Leu1189_Val1190insTer	frameshift
NC_000011.10:g.108281159del
NC_000011.9:g.108151886del
NG_009830.1:g.63328del
LRG_135:g.63328del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:108281157:TT:T

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA658822193 dbSNP: rs1555091431 VarSome

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
Gene	OMIM	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.
ATM		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	12180	19635

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.
not provided	Likely pathogenic (1)	criteria provided, single submitter	Nov 1, 2017	RCV000658623.34
Ataxia-telangiectasia syndrome	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Jan 13, 2024	RCV001261520.10

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.
Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (Perez et al. (J Hum Genet. 2020))	Ataxia-telangiectasia syndrome (Autosomal recessive inheritance)	Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia Accession: SCV001424176.3 First in ClinVar: Oct 25, 2020 Last updated: Aug 03, 2025	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Zygosity: 1 Single Heterozygote Sex: male Comment on evidence: "Unknown function" was previously submitted as the functional consequence for NM_000051.3:c.3567delT, but without providing the result of a functional assay.

Pathogenic (Jan 13, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Ataxia-telangiectasia syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004375986.3 First in ClinVar: Feb 20, 2024 Last updated: Feb 23, 2026	Publications: PubMed (3) PubMed: 23807571‚ 25614872‚ 33084218 Comment: show This sequence change creates a premature translational stop signal (p.Val1190*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 33084218). ClinVar contains an entry for this variant (Variation ID: 546687). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

Likely pathogenic (Nov 01, 2017) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV000780403.40 First in ClinVar: Jul 09, 2018 Last updated: Apr 25, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Comment:

This sequence change creates a premature translational stop signal (p.Val1190*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 33084218). ClinVar contains an entry for this variant (Variation ID: 546687). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The odyssey of complex neurogenetic disorders: From undetermined to positive.	Salinas V	American journal of medical genetics. Part C, Seminars in medical genetics	2020	PMID: 33084218
Ten new ATM alterations in Polish patients with ataxia-telangiectasia.	Podralska MJ	Molecular genetics & genomic medicine	2014	PMID: 25614872
Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.	Huang Y	Neuromolecular medicine	2013	PMID: 23807571

Text-mined citations for rs1555091431 ...

These 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 Apr 26, 2026