NM_000051.4(ATM):c.1A>G (p.Met1Val) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000051.4(ATM):c.1A>G (p.Met1Val)]

NM_000051.4(ATM):c.1A>G (p.Met1Val)

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000051.4(ATM):c.1A>G (p.Met1Val)
  • NC_000011.10:g.108227625A>G
  • NG_009830.1:g.9794A>G
  • NM_000051.3:c.1A>G
  • NM_000051.4:c.1A>GMANE SELECT
  • NM_001351834.2:c.1A>G
  • NM_001351835.2:c.1A>G
  • NM_001351836.2:c.1A>G
  • NP_000042.3:p.Met1Val
  • NP_000042.3:p.Met1Val
  • NP_001338763.1:p.Met1Val
  • NP_001338764.1:p.Met1Val
  • NP_001338765.1:p.Met1Val
  • LRG_135t1:c.1A>G
  • LRG_135:g.9794A>G
  • LRG_135p1:p.Met1Val
  • NC_000011.9:g.108098352A>G
Protein change:
dbSNP: rs730881359
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000051.3:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_000051.4:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_001351834.2:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_001351835.2:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_001351836.2:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_000051.3:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000051.4:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351835.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351836.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001339384Color Health, Inccriteria provided, single submitter
(Sep 1, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From Color Health, Inc, SCV001339384.2

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


This variant results in the loss of the translation start codon (methionine at codon 1) of the ATM gene. This variant is expected to disrupt the expression of the full-length ATM protein. The next in-frame methionine occurs at codon 94, but it has not been shown if a functional ATM protein product can be produced using p.Met94 as an alternative translation start site. This variant has been reported in trans with p.Gly2891Asp variant in an individual affected with breast cancer and mild ataxia-telangiectasia (PMID: 22146522). Cells derived from this patient showed 10-20% of kinase activity compared to normal cells. A functional study has shown that the cells transfected with this variant construct show a very low level expression of a truncated protein, probably due to the use of a downstream methionine for translation initiation (PMID: 22146522). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Nov 20, 2021

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