3-142503442-A-G

Position:

chr3-142503442-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001184.4(ATR):c.5208T>C(p.Tyr1736Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,587,382 control chromosomes in the GnomAD database, including 120,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9419 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111354 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.31

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 links:

ATR (HGNC:):

ATR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 3-142503442-A-G is Benign according to our data. Variant chr3-142503442-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 157992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-142503442-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4 linkuse as main transcript	c.5208T>C	p.Tyr1736Tyr	synonymous_variant	30/47	ENST00000350721.9	NP_001175.2	Q13535-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9 linkuse as main transcript	c.5208T>C	p.Tyr1736Tyr	synonymous_variant	30/47	1	NM_001184.4	ENSP00000343741.4		Q13535-1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51985

AN:

151962

Hom.:

9415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.353

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.360

AC:

89658

AN:

248974

Hom.:

16847

AF XY:

0.362

AC XY:

48800

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.362

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.389

AC:

558182

AN:

1435302

Hom.:

111354

Cov.:

AF XY:

0.387

AC XY:

276871

AN XY:

715200

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.321

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.342

AC:

52007

AN:

152080

Hom.:

9419

Cov.:

AF XY:

0.342

AC XY:

25397

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.354

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.381

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.397

Hom.:

18214

Bravo

AF:

0.337

Asia WGS

AF:

0.323

AC:

1119

AN:

3470

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 27, 2016	Variant summary: The c.5208C>T in ATR gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing. The variant is present in the control population dataset of ExAC at frequency of 36%. The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.00006% in this gene, suggesting that it is a benign common polymorphism. The variant of interest has been reported as Benign/Polymorphism by a clinical laboratory and a published report (Durocher et al., 2006). Taken together, based on the prevalence in general population the variant was classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -

Seckel syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.2

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over