NM_001184.4:c.5460T>C

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.5460T>C(p.Tyr1820Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,613,800 control chromosomes in the GnomAD database, including 10,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 672 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9400 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.50

Publications

16 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=-0.49).

BP6

Variant 3-142498695-A-G is Benign according to our data. Variant chr3-142498695-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 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.5460T>C	p.Tyr1820Tyr	synonymous	Exon 32 of 47	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.5268T>C	p.Tyr1756Tyr	synonymous	Exon 31 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.5460T>C	p.Tyr1820Tyr	synonymous	Exon 32 of 47	ENSP00000343741.4	Q13535-1
ATR	ENST00000513291.2	TSL:1	n.644T>C		non_coding_transcript_exon	Exon 2 of 16
ATR	ENST00000936442.1		c.5307T>C	p.Tyr1769Tyr	synonymous	Exon 31 of 46	ENSP00000606501.1

Frequencies

GnomAD3 genomes

AF:

0.0787

AC:

11966

AN:

152132

Hom.:

669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0582

Gnomad ASJ

AF:

0.0812

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0736

GnomAD2 exomes

AF:

0.0922

AC:

23126

AN:

250950

AF XY:

0.0992

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.0401

Gnomad ASJ exome

AF:

0.0794

Gnomad EAS exome

AF:

0.00136

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.0872

GnomAD4 exome

AF:

0.108

AC:

157739

AN:

1461550

Hom.:

9400

Cov.:

AF XY:

0.110

AC XY:

79853

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.0152

AC:

508

AN:

33472

American (AMR)

AF:

0.0432

AC:

1934

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0804

AC:

2102

AN:

26132

East Asian (EAS)

AF:

0.000806

AC:

AN:

39688

South Asian (SAS)

AF:

0.159

AC:

13737

AN:

86234

European-Finnish (FIN)

AF:

0.128

AC:

6815

AN:

53400

Middle Eastern (MID)

AF:

0.0684

AC:

394

AN:

5760

European-Non Finnish (NFE)

AF:

0.114

AC:

126300

AN:

1111760

Other (OTH)

AF:

0.0980

AC:

5917

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

7301

14603

21904

29206

36507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4576

9152

13728

18304

22880

<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:

0.0786

AC:

11972

AN:

152250

Hom.:

672

Cov.:

AF XY:

0.0782

AC XY:

5825

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0197

AC:

820

AN:

41554

American (AMR)

AF:

0.0582

AC:

889

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0812

AC:

282

AN:

3472

East Asian (EAS)

AF:

0.00308

AC:

AN:

5188

South Asian (SAS)

AF:

0.155

AC:

746

AN:

4824

European-Finnish (FIN)

AF:

0.133

AC:

1413

AN:

10588

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7614

AN:

68016

Other (OTH)

AF:

0.0724

AC:

153

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

557

1114

1671

2228

2785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0958

Hom.:

1108

Bravo

AF:

0.0669

Asia WGS

AF:

0.0670

AC:

233

AN:

3478

EpiCase

AF:

0.0993

EpiControl

AF:

0.103

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome (2)

not provided (2)

not specified (2)

Seckel syndrome 1 (2)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.1

(source)

DANN

Benign

0.88

PhyloP100

1.5

Mutation Taster

=96/4

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