rs35203200

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000051.4(ATM):c.7618G>A(p.Val2540Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000085 in 1,611,924 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V2540V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

ATM
NM_000051.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:21B:3

Conservation

PhyloP100: 5.65

Publications

12 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATM	NM_000051.4	MANE Select	c.7618G>A	p.Val2540Ile	missense	Exon 51 of 63	NP_000042.3
ATM	NM_001351834.2		c.7618G>A	p.Val2540Ile	missense	Exon 52 of 64	NP_001338763.1	Q13315
C11orf65	NM_001330368.2		c.641-22475C>T		intron	N/A	NP_001317297.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.7618G>A	p.Val2540Ile	missense	Exon 51 of 63	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.7618G>A	p.Val2540Ile	missense	Exon 52 of 64	ENSP00000388058.2	Q13315
C11orf65	ENST00000615746.4	TSL:1	c.*1291C>T		3_prime_UTR	Exon 13 of 13	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0164

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

251002

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000801

AC:

117

AN:

1460176

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

726360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.0000672

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.00

AC:

AN:

85922

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000972

AC:

108

AN:

1111272

Other (OTH)

AF:

0.0000829

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

AF:

0.000132

AC:

AN:

151748

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41318

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67952

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000954

Hom.:

Bravo

AF:

0.000264

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ataxia-telangiectasia syndrome (6)

not provided (5)

Familial cancer of breast (3)

Hereditary cancer-predisposing syndrome (3)

not specified (2)

Ataxia-telangiectasia syndrome;C0346153:Familial cancer of breast (1)

ATM-related cancer predisposition (1)

ATM-related disorder (1)

Breast and/or ovarian cancer (1)

Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.6

PhyloP100

5.7

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.56

REVEL

Uncertain

0.32

Sift

Benign

0.21

Sift4G

Benign

0.25

Polyphen

0.71

Vest4

0.22

MutPred

0.34

Loss of MoRF binding (P = 0.3409)

MVP

0.86

MPC

0.10

ClinPred

0.12

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.27

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.30

Position offset: 21

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