NM_000051.4:c.3403-15dupT

Variant names:

• chr11-108280970-A-AT
• rs1555091083
• NM_000051.4:c.3403-15dupT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.3403-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,467,080 control chromosomes in the GnomAD database, including 934 homozygotes. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.073 (640 hom., cov: 31)
  • Exomes 𝑓: 0.0064 (294 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.301

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-108280970-A-AT is Benign according to our data. Variant chr11-108280970-A-AT is described in ClinVar as [Benign]. Clinvar id is 235644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.3403-15dupT		intron_variant	Intron 23 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.3403-25_3403-24insT		intron_variant	Intron 23 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 7606 AN: 105064 Hom.: 631 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00191

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.00631

Gnomad EAS AF: 0.00114

Gnomad SAS AF: 0.00218

Gnomad FIN AF: 0.000319

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.0697

GnomAD3 exomes AF: 0.0206 AC: 3217 AN: 156048 Hom.: 131 AF XY: 0.0162 AC XY: 1375 AN XY: 84626

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.0235

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.00118

Gnomad SAS exome AF: 0.00176

Gnomad FIN exome AF: 0.000852

Gnomad NFE exome AF: 0.00297

Gnomad OTH exome AF: 0.0161

GnomAD4 exome AF: 0.00645 AC: 8781 AN: 1361918 Hom.: 294 Cov.: 26 AF XY: 0.00566 AC XY: 3855 AN XY: 680542

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.00493

Gnomad4 EAS exome AF: 0.000532

Gnomad4 SAS exome AF: 0.000950

Gnomad4 FIN exome AF: 0.000675

Gnomad4 NFE exome AF: 0.00170

Gnomad4 OTH exome AF: 0.0158

GnomAD4 genome AF: 0.0727 AC: 7646 AN: 105162 Hom.: 640 Cov.: 31 AF XY: 0.0711 AC XY: 3607 AN XY: 50712

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.00631

Gnomad4 EAS AF: 0.00115

Gnomad4 SAS AF: 0.00182

Gnomad4 FIN AF: 0.000319

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.0691

Bravo AF: 0.0582

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 05, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breast and/or ovarian cancer Benign:1

May 26, 2021

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ataxia-telangiectasia syndrome Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

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: rs1555091083; hg19: chr11-108151697;