11-108317539-ATTTT-ATTT

Position:

• chr11-108317539-ATTTT-ATTT

Variant summary

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

The NM_000051.4(ATM):​c.6347+31delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 125,032 control chromosomes in the GnomAD database, including 2,646 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2646 hom., cov: 24)
  • Exomes 𝑓: 0.21 (851 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.405

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]

ATM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-108317539-AT-A is Benign according to our data. Variant chr11-108317539-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 522241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108317539-AT-A is described in Lovd as [Benign]. Variant chr11-108317539-AT-A is described in Lovd as [Likely_benign]. Variant chr11-108317539-AT-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4	c.6347+31delT		intron_variant		ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.6347+31delT		intron_variant			NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 15300 AN: 125012 Hom.: 2643 Cov.: 24

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.00256

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0339

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.00405

Gnomad FIN AF: 0.00201

Gnomad MID AF: 0.0391

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0958

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.207 AC: 176126 AN: 851688 Hom.: 851 Cov.: 0 AF XY: 0.209 AC XY: 87545 AN XY: 418412

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.123 AC: 15317 AN: 125032 Hom.: 2646 Cov.: 24 AF XY: 0.119 AC XY: 7133 AN XY: 59914

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.0624

Gnomad4 ASJ AF: 0.0339

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.00356

Gnomad4 FIN AF: 0.00201

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.0951

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ataxia-telangiectasia syndrome Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Jun 09, 2015	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2019

- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Jun 26, 2017

- -

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: rs58978479; hg19: chr11-108188266;