11-108292760-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000051.4(ATM):c.4578C>T(p.Pro1526Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 1,613,832 control chromosomes in the GnomAD database, including 1,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1526P) has been classified as Likely benign. The gene ATM is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.031 ( 123 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1737 hom. )

Consequence

ATM
NM_000051.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:29

Conservation

PhyloP100: -0.292

Publications

50 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

Specifications for ATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-108292760-C-T is Benign according to our data. Variant chr11-108292760-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 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.4578C>T	p.Pro1526Pro	synonymous	Exon 30 of 63	NP_000042.3
	ATM	NM_001351834.2		c.4578C>T	p.Pro1526Pro	synonymous	Exon 31 of 64	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.4578C>T	p.Pro1526Pro	synonymous	Exon 30 of 63	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.4578C>T	p.Pro1526Pro	synonymous	Exon 31 of 64	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.4437-2167C>T		intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4727

AN:

152024

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00918

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0293

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0249

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0326

AC:

8190

AN:

251362

AF XY:

0.0323

show subpopulations

Gnomad AFR exome

AF:

0.00806

Gnomad AMR exome

AF:

0.0310

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0502

Gnomad OTH exome

AF:

0.0356

GnomAD4 exome

AF:

0.0452

AC:

66121

AN:

1461690

Hom.:

1737

Cov.:

AF XY:

0.0441

AC XY:

32045

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.00621

AC:

208

AN:

33476

American (AMR)

AF:

0.0307

AC:

1373

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0134

AC:

349

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0139

AC:

1199

AN:

86254

European-Finnish (FIN)

AF:

0.0280

AC:

1495

AN:

53416

Middle Eastern (MID)

AF:

0.00625

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0532

AC:

59142

AN:

1111880

Other (OTH)

AF:

0.0384

AC:

2319

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

3350

6699

10049

13398

16748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2146

4292

6438

8584

10730

<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:

0.0311

AC:

4727

AN:

152142

Hom.:

123

Cov.:

AF XY:

0.0291

AC XY:

2167

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00916

AC:

380

AN:

41496

American (AMR)

AF:

0.0291

AC:

445

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0129

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0249

AC:

264

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0511

AC:

3472

AN:

67988

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

238

476

715

953

1191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0439

Hom.:

378

Bravo

AF:

0.0296

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0486

EpiControl

AF:

0.0407

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (11)

Ataxia-telangiectasia syndrome (6)

Hereditary cancer-predisposing syndrome (5)

not provided (3)

Familial cancer of breast (2)

Hereditary breast ovarian cancer syndrome (1)

Malignant tumor of breast (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.5

(source)

DANN

Benign

0.48

PhyloP100

-0.29

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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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