11-108325985-CATTATTATT-CATTATT

Variant names:

• chr11-108325985-CATT-C
• rs3212322
• NM_000051.4:c.6808-60_6808-58delATT

Variant summary

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

The NM_000051.4(ATM):​c.6808-60_6808-58delATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,535,810 control chromosomes in the GnomAD database, including 237,239 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20285 hom., cov: 0)
  • Exomes 𝑓: 0.56 (216954 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 3.05

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]

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-108325985-CATT-C is Benign according to our data. Variant chr11-108325985-CATT-C is described in ClinVar as [Benign]. Clinvar id is 633055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108325985-CATT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.6808-60_6808-58delATT		intron_variant	Intron 46 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.6808-72_6808-70delATT		intron_variant	Intron 46 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75883 AN: 151486 Hom.: 20272 Cov.: 0

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.556 AC: 769167 AN: 1384206 Hom.: 216954 AF XY: 0.559 AC XY: 386533 AN XY: 691182

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.501 AC: 75916 AN: 151604 Hom.: 20285 Cov.: 0 AF XY: 0.509 AC XY: 37683 AN XY: 74028

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.545

Alfa AF: 0.527 Hom.: 2658

Bravo AF: 0.489

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 09, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The ATM c.6808-60_6808-58delATT variant involves the deletions of a stretch of three intronic nucleotides. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in gnomAD in 15100/30750 control chromosomes at a frequency of 0.4910569, which is approximately 124 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528), suggesting this variant is a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Ataxia-telangiectasia syndrome Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs3212322; hg19: chr11-108196712;