Submissions for variant NM_000051.4(ATM):c.4167A>G (p.Thr1389=)

gnomAD frequency: 0.00009  dbSNP: rs183214437

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212010	SCV000167088	benign	not specified	2014-03-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000123745	SCV000212975	benign	Hereditary cancer-predisposing syndrome	2014-10-10	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000988683	SCV000282955	likely benign	Ataxia-telangiectasia syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000123745	SCV000537429	likely benign	Hereditary cancer-predisposing syndrome	2016-07-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000212010	SCV000694274	likely benign	not specified	2019-08-20	criteria provided, single submitter	clinical testing
Mendelics	RCV000988683	SCV001138500	likely benign	Ataxia-telangiectasia syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212010	SCV002065751	likely benign	not specified	2021-11-22	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000123745	SCV002529052	likely benign	Hereditary cancer-predisposing syndrome	2021-01-26	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV003390810	SCV004133256	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	ATM: BP4, BP7
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003390810	SCV004221045	likely benign	not provided	2021-10-14	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000123745	SCV005045432	benign	Hereditary cancer-predisposing syndrome	2024-02-27	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589618	SCV005083964	benign	Familial cancer of breast	2024-05-16	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000212010	SCV001549118	benign	not specified		no assertion criteria provided	clinical testing	The ATM p.Thr1389= variant was not identified in the literature nor was it identified in the Genesight-COGR, Cosmic, MutDB, LOVD 3.0, ATM-LOVD, databases. The variant was identified in dbSNP (ID: rs183214437) as “with other allele”, in ClinVar and Clinvitae databases as benign by GeneDx and Ambry Genetics; and likely benign by Invitae, and Color Genomics Inc.). The variant was identified in control databases in 29 of 277012 chromosomes at a frequency of 0.0001 in the following populations: African in 1 of 24024 chromosomes (freq. 0.00004), Latino in 7 of 34400 chromosomes (freq. 0.0002), European Non-Finnish in 18 of 126560 chromosomes (freq. 0.0001), Other in 3of 6458 chromosomes (freq. 0.0005), but was not seen in Ashkenazi Jewish, East Asian , European Finnish, and South Asian populations, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The p.Thr1389= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.