3-142558694-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001184.4(ATR):c.1815T>C(p.Asp605Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,611,750 control chromosomes in the GnomAD database, including 120,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9172 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111042 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.576

Publications

40 publications found

Variant links:

Genes affected

ATR (HGNC:882): (ATR serine/threonine kinase) The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

ATR Gene-Disease associations (from GenCC):

Seckel syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Ambry Genetics
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial prostate carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-142558694-A-G is Benign according to our data. Variant chr3-142558694-A-G is described in ClinVar as Benign. ClinVar VariationId is 157966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.576 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	NM_001184.4	MANE Select	c.1815T>C	p.Asp605Asp	synonymous	Exon 8 of 47	NP_001175.2
	ATR	NM_001354579.2		c.1623T>C	p.Asp541Asp	synonymous	Exon 7 of 46	NP_001341508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ATR	ENST00000350721.9	TSL:1 MANE Select	c.1815T>C	p.Asp605Asp	synonymous	Exon 8 of 47	ENSP00000343741.4
ATR	ENST00000661310.1		c.1623T>C	p.Asp541Asp	synonymous	Exon 7 of 46	ENSP00000499589.1
ATR	ENST00000515149.3	TSL:3	n.*589T>C		non_coding_transcript_exon	Exon 7 of 18	ENSP00000425897.3

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51293

AN:

151946

Hom.:

9167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.370

GnomAD2 exomes

AF:

0.357

AC:

89555

AN:

251068

AF XY:

0.359

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.386

AC:

563455

AN:

1459686

Hom.:

111042

Cov.:

AF XY:

0.384

AC XY:

278971

AN XY:

726228

show subpopulations

African (AFR)

AF:

0.194

AC:

6493

AN:

33438

American (AMR)

AF:

0.322

AC:

14361

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

11732

AN:

26078

East Asian (EAS)

AF:

0.325

AC:

12850

AN:

39532

South Asian (SAS)

AF:

0.262

AC:

22573

AN:

86102

European-Finnish (FIN)

AF:

0.377

AC:

20121

AN:

53320

Middle Eastern (MID)

AF:

0.392

AC:

2257

AN:

5754

European-Non Finnish (NFE)

AF:

0.405

AC:

450233

AN:

1110540

Other (OTH)

AF:

0.379

AC:

22835

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16638

33275

49913

66550

83188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13830

27660

41490

55320

69150

<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:

0.337

AC:

51316

AN:

152064

Hom.:

9172

Cov.:

AF XY:

0.337

AC XY:

25075

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.202

AC:

8362

AN:

41488

American (AMR)

AF:

0.352

AC:

5380

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1533

AN:

3468

East Asian (EAS)

AF:

0.354

AC:

1836

AN:

5184

South Asian (SAS)

AF:

0.272

AC:

1313

AN:

4830

European-Finnish (FIN)

AF:

0.372

AC:

3924

AN:

10542

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.405

AC:

27548

AN:

67964

Other (OTH)

AF:

0.372

AC:

787

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1707

3413

5120

6826

8533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.384

Hom.:

9188

Bravo

AF:

0.334

Asia WGS

AF:

0.322

AC:

1118

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Dec 20, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 02, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

Benign:2

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Seckel syndrome 1

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Feb 08, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary cancer-predisposing syndrome

Benign:1

Jul 10, 2025

GeneKor MSA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.6

(source)

DANN

Benign

0.49

PhyloP100

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over