NM_000051.4:c.4437-9C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000051.4(ATM):c.4437-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,458,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATM
NM_000051.4 intron

Scores

Splicing: ADA: 0.00001971

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.131

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-108292610-C-T is Benign according to our data. Variant chr11-108292610-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 216215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.4437-9C>T		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.4437-9C>T		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.4437-9C>T	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.4437-9C>T	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.4437-2317C>T	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

248642

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1458236

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725492

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33122

American (AMR)

AF:

0.0000228

AC:

AN:

43946

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.00

AC:

AN:

85644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1110680

Other (OTH)

AF:

0.0000166

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000199

AC:

AN:

151048

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41100

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67832

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000354

Hom.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ataxia-telangiectasia syndrome (3)

not specified (3)

Familial cancer of breast (2)

ATM-related disorder (1)

Hereditary cancer-predisposing syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.9

(source)

DANN

Benign

0.27

PhyloP100

-0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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