Variant chr3-142558733-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001184.4(ATR):c.1776T>A(p.Gly592=) 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 (★★).

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:12

Conservation

PhyloP100: -0.264

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 157965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-142558733-A-T is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4 linkuse as main transcript	c.1776T>A	p.Gly592=	synonymous_variant	8/47	ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9 linkuse as main transcript	c.1776T>A	p.Gly592=	synonymous_variant	8/47	1	NM_001184.4	ENSP00000343741	P1	Q13535-1

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

GnomAD3 exomes

AF:

0.546

AC:

136880

AN:

250500

Hom.:

38556

AF XY:

0.542

AC XY:

73359

AN XY:

135456

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 SAS exome

AF:

0.432

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

Gnomad4 AFR exome

AF:

0.805

Gnomad4 AMR exome

AF:

0.463

Gnomad4 ASJ exome

AF:

0.561

Gnomad4 EAS exome

AF:

0.444

Gnomad4 SAS exome

AF:

0.433

Gnomad4 FIN exome

AF:

0.548

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.626

AC:

95163

AN:

151904

Hom.:

30789

Cov.:

AF XY:

0.618

AC XY:

45910

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.794

Gnomad4 AMR

AF:

0.533

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.443

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.587

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.597

Hom.:

8897

Bravo

AF:

0.634

Asia WGS

AF:

0.505

AC:

1755

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 20, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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.1776T>A variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 4/4 in silico tools via Alamut predict the variant to eliminate a cryptic splice donor site, thereby potential resulting in a protective effect on normal splicing. The variant was observed in the large, broad control population, ExAC, with an allele frequency of 55% which includes 19,239 homozygous occurrences. Therefore this synonymous variant is the major allele and has been classified as Benign. -

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	Jul 14, 2021	- -

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.6

DANN

Benign

0.67

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