rs79701258

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000051.4(ATM):c.3403-15T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 151,836 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 201 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 190 hom. )

Failed GnomAD Quality Control

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: 1.34

Publications

3 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 Gene-Disease associations (from GenCC):

ATM-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
ataxia telangiectasia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
gastric carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-108280980-T-A is Benign according to our data. Variant chr11-108280980-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.3403-15T>A		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3403-15T>A		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.3403-15T>A	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.3403-15T>A	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.3403-15T>A	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4237

AN:

151718

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0943

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.0000952

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.0130

GnomAD2 exomes

AF:

0.00956

AC:

2217

AN:

231976

AF XY:

0.00775

show subpopulations

Gnomad AFR exome

AF:

0.0993

Gnomad AMR exome

AF:

0.00625

Gnomad ASJ exome

AF:

0.000219

Gnomad EAS exome

AF:

0.00878

Gnomad FIN exome

AF:

0.000247

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00435

AC:

6109

AN:

1405244

Hom.:

190

Cov.:

AF XY:

0.00413

AC XY:

2890

AN XY:

700264

show subpopulations

African (AFR)

AF:

0.0952

AC:

3008

AN:

31596

American (AMR)

AF:

0.00677

AC:

282

AN:

41646

Ashkenazi Jewish (ASJ)

AF:

0.000279

AC:

AN:

25090

East Asian (EAS)

AF:

0.0186

AC:

729

AN:

39212

South Asian (SAS)

AF:

0.00890

AC:

723

AN:

81208

European-Finnish (FIN)

AF:

0.000291

AC:

AN:

51634

Middle Eastern (MID)

AF:

0.00978

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.000766

AC:

820

AN:

1071150

Other (OTH)

AF:

0.00810

AC:

471

AN:

58184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

250

500

751

1001

1251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0279

AC:

4243

AN:

151836

Hom.:

201

Cov.:

AF XY:

0.0268

AC XY:

1992

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.0941

AC:

3895

AN:

41390

American (AMR)

AF:

0.0113

AC:

173

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0110

AC:

AN:

5182

South Asian (SAS)

AF:

0.00809

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000952

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000707

AC:

AN:

67898

Other (OTH)

AF:

0.0128

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

198

396

593

791

989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0237

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Ataxia-telangiectasia syndrome (5)

Hereditary cancer-predisposing syndrome (3)

not provided (2)

Breast and/or ovarian cancer (1)

Familial cancer of breast (1)

Malignant tumor of breast (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.57

(source)

DANN

Benign

0.081

PhyloP100

1.3

Mutation Taster

=21/79

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over