rs3218711

Variant names:

• chr11-108365537-C-G
• rs3218711
• NM_000051.4:c.*29C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000051.4(ATM):​c.*29C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,607,046 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (35 hom.)
• Consequence: ATM NM_000051.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.50

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-108365537-C-G is Benign according to our data. Variant chr11-108365537-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 302255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108365537-C-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.006 (913/152266) while in subpopulation EAS AF= 0.0106 (55/5184). AF 95% confidence interval is 0.00837. There are 6 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.*29C>G		3_prime_UTR_variant	Exon 63 of 63	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.*29C>G		3_prime_UTR_variant	Exon 63 of 63		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 914 AN: 152148 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00777

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00511 AC: 1230 AN: 240542 Hom.: 4 AF XY: 0.00486 AC XY: 631 AN XY: 129968

Gnomad AFR exome AF: 0.00774

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.00303

Gnomad EAS exome AF: 0.0119

Gnomad SAS exome AF: 0.00148

Gnomad FIN exome AF: 0.000612

Gnomad NFE exome AF: 0.00687

Gnomad OTH exome AF: 0.00471

GnomAD4 exome AF: 0.00687 AC: 9999 AN: 1454780 Hom.: 35 Cov.: 30 AF XY: 0.00665 AC XY: 4809 AN XY: 723404

Gnomad4 AFR exome AF: 0.00772

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.00342

Gnomad4 EAS exome AF: 0.00701

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.000602

Gnomad4 NFE exome AF: 0.00776

Gnomad4 OTH exome AF: 0.00894

GnomAD4 genome AF: 0.00600 AC: 913 AN: 152266 Hom.: 6 Cov.: 32 AF XY: 0.00561 AC XY: 418 AN XY: 74458

Gnomad4 AFR AF: 0.00778

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00657

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00484 Hom.: 0

Bravo AF: 0.00632

Asia WGS AF: 0.00924 AC: 32 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ataxia-telangiectasia syndrome Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.49

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: rs3218711; hg19: chr11-108236264; COSMIC: COSV99590269; COSMIC: COSV99590269;