3-142547597-C-T

Position:

• chr3-142547597-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001184.4(ATR):​c.3357+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,061,372 control chromosomes in the GnomAD database, including 20,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2314 hom., cov: 32)
  • Exomes 𝑓: 0.19 (17712 hom.)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-142547597-C-T is Benign according to our data. Variant chr3-142547597-C-T is described in ClinVar as [Benign]. Clinvar id is 1266052.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4	c.3357+128G>A		intron_variant		ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.3357+128G>A		intron_variant		1	NM_001184.4	ENSP00000343741	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25006 AN: 151846 Hom.: 2318 Cov.: 32

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.192 AC: 174642 AN: 909410 Hom.: 17712 AF XY: 0.190 AC XY: 88023 AN XY: 462974

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.165 AC: 25001 AN: 151962 Hom.: 2314 Cov.: 32 AF XY: 0.167 AC XY: 12381 AN XY: 74256

Gnomad4 AFR AF: 0.0700

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.167

Alfa AF: 0.187 Hom.: 1287

Bravo AF: 0.161

Asia WGS AF: 0.132 AC: 457 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs13091637; hg19: chr3-142266439; COSMIC: COSV63385558;