NM_000051.4:c.6808-60_6808-58delATT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000051.4(ATM):c.6808-60_6808-58delATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,535,810 control chromosomes in the GnomAD database, including 237,239 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20285 hom., cov: 0)

Exomes 𝑓: 0.56 ( 216954 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.05

Publications

1 publications found

Variant links:

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ATM links:

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

C11orf65 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-108325985-CATT-C is Benign according to our data. Variant chr11-108325985-CATT-C is described in ClinVar as [Benign]. Clinvar id is 633055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4 link	c.6808-60_6808-58delATT		intron_variant	Intron 46 of 62	ENST00000675843.1	NP_000042.3	Q13315A0A024R3C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 link	c.6808-72_6808-70delATT		intron_variant	Intron 46 of 62		NM_000051.4	ENSP00000501606.1		Q13315

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

75883

AN:

151486

Hom.:

20272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.642

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.544

GnomAD4 exome

AF:

0.556

AC:

769167

AN:

1384206

Hom.:

216954

AF XY:

0.559

AC XY:

386533

AN XY:

691182

show subpopulations

African (AFR)

AF:

0.293

AC:

9318

AN:

31842

American (AMR)

AF:

0.629

AC:

26873

AN:

42714

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

15583

AN:

25452

East Asian (EAS)

AF:

0.415

AC:

16153

AN:

38952

South Asian (SAS)

AF:

0.598

AC:

49650

AN:

83066

European-Finnish (FIN)

AF:

0.626

AC:

31549

AN:

50426

Middle Eastern (MID)

AF:

0.713

AC:

3741

AN:

5244

European-Non Finnish (NFE)

AF:

0.557

AC:

584530

AN:

1048768

Other (OTH)

AF:

0.550

AC:

31770

AN:

57742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

16817

33633

50450

67266

84083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.501

AC:

75916

AN:

151604

Hom.:

20285

Cov.:

AF XY:

0.509

AC XY:

37683

AN XY:

74028

show subpopulations

African (AFR)

AF:

0.300

AC:

12418

AN:

41354

American (AMR)

AF:

0.608

AC:

9252

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2221

AN:

3468

East Asian (EAS)

AF:

0.414

AC:

2136

AN:

5158

South Asian (SAS)

AF:

0.603

AC:

2900

AN:

4808

European-Finnish (FIN)

AF:

0.629

AC:

6587

AN:

10480

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38461

AN:

67818

Other (OTH)

AF:

0.545

AC:

1146

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1851

3702

5554

7405

9256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.527

Hom.:

2658

Bravo

AF:

0.489

Asia WGS

AF:

0.533

AC:

1852

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The ATM c.6808-60_6808-58delATT variant involves the deletions of a stretch of three intronic nucleotides. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in gnomAD in 15100/30750 control chromosomes at a frequency of 0.4910569, which is approximately 124 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528), suggesting this variant is a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Ataxia-telangiectasia syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_000051.4:c.6808-60_6808-58delATT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over