NM_001184.4:c.1776T>A

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.1776T>A(p.Gly592Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,609,390 control chromosomes in the GnomAD database, including 272,130 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. G592G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.63 ( 30789 hom., cov: 31)

Exomes 𝑓: 0.57 ( 241341 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.264

Publications

49 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: G2P, Ambry Genetics, Illumina
familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: 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=-0.6).

BP6

Variant 3-142558733-A-T is Benign according to our data. Variant chr3-142558733-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 157965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.264 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	NM_001184.4	MANE Select	c.1776T>A	p.Gly592Gly	synonymous	Exon 8 of 47	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.1584T>A	p.Gly528Gly	synonymous	Exon 7 of 46	NP_001341508.1	Q13535-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATR	ENST00000350721.9	TSL:1 MANE Select	c.1776T>A	p.Gly592Gly	synonymous	Exon 8 of 47	ENSP00000343741.4	Q13535-1
ATR	ENST00000661310.1		c.1584T>A	p.Gly528Gly	synonymous	Exon 7 of 46	ENSP00000499589.1	Q13535-2
ATR	ENST00000936443.1		c.1776T>A	p.Gly592Gly	synonymous	Exon 8 of 46	ENSP00000606502.1

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95066

AN:

151788

Hom.:

30738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.679

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.621

GnomAD2 exomes

AF:

0.546

AC:

136880

AN:

250500

AF XY:

0.542

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.564

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.579

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.572

AC:

833137

AN:

1457486

Hom.:

241341

Cov.:

AF XY:

0.567

AC XY:

411520

AN XY:

725186

show subpopulations

African (AFR)

AF:

0.805

AC:

26859

AN:

33380

American (AMR)

AF:

0.463

AC:

20590

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

14609

AN:

26046

East Asian (EAS)

AF:

0.444

AC:

17528

AN:

39446

South Asian (SAS)

AF:

0.433

AC:

37271

AN:

85998

European-Finnish (FIN)

AF:

0.548

AC:

29162

AN:

53230

Middle Eastern (MID)

AF:

0.563

AC:

3242

AN:

5758

European-Non Finnish (NFE)

AF:

0.586

AC:

649314

AN:

1108942

Other (OTH)

AF:

0.574

AC:

34562

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

16430

32860

49290

65720

82150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17802

35604

53406

71208

89010

<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:

0.626

AC:

95163

AN:

151904

Hom.:

30789

Cov.:

AF XY:

0.618

AC XY:

45910

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.794

AC:

32907

AN:

41430

American (AMR)

AF:

0.533

AC:

8139

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1945

AN:

3470

East Asian (EAS)

AF:

0.465

AC:

2401

AN:

5164

South Asian (SAS)

AF:

0.443

AC:

2138

AN:

4822

European-Finnish (FIN)

AF:

0.539

AC:

5664

AN:

10500

Middle Eastern (MID)

AF:

0.606

AC:

177

AN:

292

European-Non Finnish (NFE)

AF:

0.587

AC:

39852

AN:

67938

Other (OTH)

AF:

0.625

AC:

1321

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1702

3405

5107

6810

8512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.597

Hom.:

8897

Bravo

AF:

0.634

Asia WGS

AF:

0.505

AC:

1755

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (4)

Seckel syndrome 1 (2)

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.6

(source)

DANN

Benign

0.67

PhyloP100

-0.26

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

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