rs13091637

Variant names:

• chr3-142547597-C-T
• rs13091637
• NM_001184.4:c.3357+128G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.3357+128G>A		intron	N/A	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.3165+128G>A		intron	N/A	NP_001341508.1	Q13535-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	ENST00000350721.9	TSL:1 MANE Select	c.3357+128G>A		intron	N/A	ENSP00000343741.4	Q13535-1
	ATR	ENST00000936442.1		c.3204+128G>A		intron	N/A	ENSP00000606501.1
	ATR	ENST00000661310.1		c.3165+128G>A		intron	N/A	ENSP00000499589.1	Q13535-2

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

African (AFR) AF: 0.0616 AC: 1269 AN: 20594

American (AMR) AF: 0.201 AC: 4979 AN: 24724

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 4864 AN: 20070

East Asian (EAS) AF: 0.165 AC: 5481 AN: 33288

South Asian (SAS) AF: 0.122 AC: 7532 AN: 61602

European-Finnish (FIN) AF: 0.225 AC: 7781 AN: 34598

Middle Eastern (MID) AF: 0.164 AC: 600 AN: 3656

European-Non Finnish (NFE) AF: 0.200 AC: 134089 AN: 669234

Other (OTH) AF: 0.193 AC: 8047 AN: 41644

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

African (AFR) AF: 0.0700 AC: 2899 AN: 41438

American (AMR) AF: 0.207 AC: 3155 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 827 AN: 3464

East Asian (EAS) AF: 0.154 AC: 799 AN: 5186

South Asian (SAS) AF: 0.132 AC: 636 AN: 4820

European-Finnish (FIN) AF: 0.226 AC: 2383 AN: 10522

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13799 AN: 67948

Other (OTH) AF: 0.167 AC: 352 AN: 2108

Alfa AF: 0.189 Hom.: 1452

Bravo AF: 0.161

Asia WGS AF: 0.132 AC: 457 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.84
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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