NM_000051.4(ATM):c.8998C>T (p.Gln3000Ter) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Sep 11, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000051.4(ATM):c.8998C>T (p.Gln3000Ter)]

NM_000051.4(ATM):c.8998C>T (p.Gln3000Ter)

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000051.4(ATM):c.8998C>T (p.Gln3000Ter)
  • NC_000011.10:g.108365335C>T
  • NG_009830.1:g.147504C>T
  • NG_054724.1:g.109498G>A
  • NM_000051.4:c.8998C>TMANE SELECT
  • NM_001330368.2:c.640+20585G>A
  • NM_001351110.2:c.694+20585G>A
  • NM_001351834.2:c.8998C>T
  • NP_000042.3:p.Gln3000Ter
  • NP_001338763.1:p.Gln3000Ter
  • LRG_135t1:c.8998C>T
  • LRG_135:g.147504C>T
  • NC_000011.9:g.108236062C>T
  • NC_000011.9:g.108236062C>T
  • NM_000051.3:c.8998C>T
  • p.Q3000*
Protein change:
dbSNP: rs587781698
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001330368.2:c.640+20585G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.694+20585G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.8998C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.8998C>T - nonsense - [Sequence Ontology: SO:0001587]


Ataxia-telangiectasia syndrome (AT)
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000678101Counsylcriteria provided, single submitter
Likely pathogenic
(Feb 9, 2017)
unknownclinical testing

Citation Link,

SCV001408167Invitaecriteria provided, single submitter
(Sep 11, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing



Mutations associated with variant phenotypes in ataxia-telangiectasia.

McConville CM, Stankovic T, Byrd PJ, McGuire GM, Yao QY, Lennox GG, Taylor MR.

Am J Hum Genet. 1996 Aug;59(2):320-30.

PubMed [citation]

Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families.

Chessa L, Piane M, Magliozzi M, Torrente I, Savio C, Lulli P, De Luca A, Dallapiccola B.

Ann Hum Genet. 2009 Sep;73(Pt 5):532-9. doi: 10.1111/j.1469-1809.2009.00535.x.

PubMed [citation]
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000678101.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001408167.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


This sequence change results in a premature translational stop signal in the ATM gene (p.Gln3000*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 57 amino acids of the ATM protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 141373). This variant disrupts the C-terminus of the ATM protein. Other variant(s) that disrupt this region (p.Arg3047*) have been determined to be pathogenic (PMID: 8755918, 19691550, 18560558, 10980530, 26628246). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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